Skip to main content
NCBI home page
Current Urology logoLink to Current Urology
. 2026 Jan 29;20(3):174–179. doi: 10.1097/CU9.0000000000000323

Interleukin-11: A pivotal player and potential therapeutic target in prostate cancer

Jinghua Zhong a,b,c,d, Xiaolu Duan a,b,c,d, Ziyi Wei e, Wei Zhu a,b,c,d, Zhijian Zhao a,b,c,d,*, Guohua Zeng a,b,c,d,*
PMCID: PMC13068482  PMID: 41969323

Abstract

Interleukin-11 (IL-11), a pleiotropic cytokine belonging to the interleukin-6 (IL-6) family, is implicated in the initiation and progression of various malignancies. Recent studies revealed that IL-11 plays multifaceted roles in prostate cancer, contributing to tumor cell proliferation, castration resistance, bone metastasis, and chemotherapeutic resistance. Interleukin-11 has emerged as a promising target for both diagnostic and therapeutic strategies. This review outlines the molecular structure and biological functions of IL-11; summarizes its role in early diagnosis, prognostic evaluation, tumor progression, and therapeutic intervention for prostate cancer; and explores its potential as a novel therapeutic target.

Keywords: Interleukin-11, Prostate cancer, Diagnosis, Bone metastasis, Chemotherapeutic resistance, Target therapy

1. Introduction

Prostate cancer (PCa) is the second most common cancer in men worldwide, with both incidence and mortality rates showing a steady upward trend.[1–3] According to estimates from the American Cancer Society, PCa will account for approximately 30% of all newly diagnosed cancers in men and 11% of male cancer-related deaths by 2025, ranking second only to lung cancer in mortality.[3] In the United States, approximately 6.8% of patients are diagnosed with metastatic PCa at the initial presentation, with a 5-year survival rate of only 31%.[4]

Interleukin-11 (IL-11), a member of the interleukin-6 (IL-6) cytokine family,[5,6] has been implicated in the initiation, progression, and metastasis of multiple malignancies, including breast, lung, and colorectal cancers,[7–9] and is widely recognized as a pro-oncogenic mediator. Emerging evidence suggests that IL-11 may serve as a potential biomarker and therapeutic target for PCa. In this review, the role of IL-11 is summarized in the diagnosis and prognostic evaluation of PCa, its potential mechanisms in tumor development and progression, and the recent advances in therapeutic strategies targeting IL-11.

2. Molecular architecture and biological roles of interleukin-11 and interleukin-11 receptor alpha

Interleukin-11 is a member of the IL-6 cytokine family, which includes IL-6, leukemia inhibitory factor, oncostatin M, ciliary neurotrophic factor, cardiotrophin-1, cardiotrophin-like cytokine, neurogenin, interleukin-27, and interleukin-31.[5,6] Paul et al. initially purified and cloned IL-11 from the supernatant of primate bone marrow stromal cells. Interleukin-11, located on chromosome 19q13.3–13.4, contains 5 coding exons and encodes a protein of 178 amino acids with a molecular weight of approximately 19 kDa.[10,11] Interleukin-11 exists as a monomer and folds into a 4-helical bundle structure (Fig. 1). Its promoter region contains multiple cis-regulatory elements, including binding sites for transforming growth factor-β1, specificity protein-1, signal transducer and activator of transcription 3 and 5a, CCAAT Transcription Factor/Nuclear Factor 1, and interferon-1, as well as a putative nuclear factor-kappa B response element.[10,12] Although IL-11 shares a similar overall topology with other IL-6 family cytokines, such as IL-6 and leukemia inhibitory factor, distinct differences exist in its receptor-binding properties.[13]

Figure 1.

Figure 1.

Open in a new tab

IL-11 3D structure (PDB ID: 4mhl). The 4 α-helical monomeric bundles (A, B, C, and D) are indicated in different colors. IL-11 = interleukin-11.

The human IL-11 receptor alpha (IL-11Rα) gene, located on chromosome 9p13, spans approximately 10 kb and comprises 13 exons.[14] Two isoforms of IL-11Rα have been identified: one containing a cytoplasmic domain and the other lacking this domain.[15] Interleukin-11 receptor alpha is expressed in a variety of organs, including the brain, bone, lung, and kidney, as well as in diverse cell types such as macrophages, osteoblasts, and osteoclasts.[16–18] During the initiation of signal transduction, IL-11 first binds to its specific membrane-bound receptor, IL-11Rα, to form a receptor-ligand tetramer.[19] This complex is subsequently associated with the common signal-transducing receptor of the IL-6 cytokine family, glycoprotein 130 (gp130), in a 2:2:2 stoichiometry to assemble a functional hexameric signaling complex. Through this hexameric complex, IL-11 predominantly exerts its pleiotropic biological functions by activating the Phosphoinositide 3-kinase (PI3K)/Protein kinase B (AKT), Rat sarcoma (Ras)/Rapidly accelerated fibrosarcoma (Raf)/Mitogen-activated protein kinase (MAPK), and Janus kinase (JAK)/Signal Transducer and Activator of Tanscription (STAT3) signaling cascades, a process referred to as the classical IL-11 signaling pathway.[20–22] Furthermore, membrane-bound IL-11R can be cleaved by ADAM10, a metalloproteinase, to generate soluble IL-11R (sIL-11R), which is released extracellularly. Free sIL-11R can bind to IL-11 in the extracellular milieu and subsequently associate with gp130-expressing cells to activate downstream signaling pathways. This process is referred to as the trans-signaling pathway.[23] Glycoprotein 130 is ubiquitously expressed in nearly all human cell types and is a critical contributor to cancer biology.[24–29] Importantly, trans-signaling expands the functional spectrum of IL-11 beyond that of cells with membrane-bound IL-11R, potentially broadening the functional scope of IL-11. However, the biological functions of the IL-11 trans-signaling pathway remain unclear. Figure 2 shows the canonical downstream signaling pathways of IL-11.

Figure 2.

Figure 2.

Open in a new tab

The schematic of the IL-11 signal transduction pathway. IL-11 activates 3 canonical intracellular downstream signaling pathways, PI3K/AKT, Ras/Raf/MAPK, and JAK/STAT3, through both classical and trans-signaling pathways. IL-11 = interleukin-11; JAK/STAT3 = janus kinase/signal transducer and activator of transcription; PI3K/AKT = phosphoinositide 3-kinase/protein kinase B; Ras/Raf/MAPK = rat sarcoma/rapidly accelerated fibrosarcoma/mitogen-activated protein kinase.

Glycoprotein 130 is ubiquitously expressed in almost all human cell types[24,25] and plays a pivotal role in tumorigenesis, making it an attractive target for cancer therapy.[26–29]

Multiple cytokines in the IL-6 family, including IL-11, have been shown to play pivotal regulatory roles in bone development and homeostasis.[30] The expression of IL-11Rα in both osteoblastic and osteoclastic lineages suggests that IL-11 participates in modulating the functions of osteoblasts, osteocytes, and osteoclasts, thereby contributing to the dynamic process of bone remodeling.[17,31] Consequently, IL-11 has emerged as a potential therapeutic target for primary bone malignancies, such as osteosarcoma, and secondary bone metastases derived from solid tumors, including prostate and breast cancers.[32–36]

3. The role of interleukin-11 in the diagnosis and prognostic evaluation of prostate cancer

The IL-11/IL-11Rα signaling axis has emerged as a promising target for the diagnosis and prognostic assessment of PCa. Campbell et al.[37] demonstrated via enzyme-linked immunosorbent assay (ELISA) that the extracellular secretion levels of IL-11 in PCa cell line (DU145) were significantly higher than those in the normal prostate epithelial cell line (97.4 ± 1.6 vs. 57.4 ± 5.1 pg/105 cells). Similarly, IL-11Rα expression detected by immunohistochemistry staining was upregulated in high-grade prostatic intraepithelial neoplasia and invasive PCa relative to normal prostate tissue and benign prostatic hyperplasia. However, no significant correlation was observed between IL-11Rα expression and Gleason score.[37] Notably, using ELISA analysis, Furuya et al. reported that IL-11 levels were significantly elevated in individuals with hormone-refractory PCa compared with patients with untreated PCa (27.4 ± 33.1 vs. 15.1 ± 16.5 pg/mL, p = 0.027).[38] Using ELISA, Chen et al. also found that serum IL-11 concentrations were significantly elevated in patients with metastatic PCa via ELISA analysis.[39] Furthermore, increased IL-11 levels were correlated with higher Gleason scores and elevated prostate-specific antigen levels.[39] Therefore, IL-11 appears to be associated with more aggressive pathological subtypes of PCa, and it may be feasible to aid in PCa diagnosis or the assessment of prognosis in patients with PCa by detecting IL-11 levels in pathological tissues or serum.

Wu et al.[40] designed a radiolabeled molecular probe with a nonapeptide structure, 99mTc-diethylenetriaminepentaacetic acid (DTPA)-c(CGRRAGGSC), specifically targeting IL-11Rα expressed on both the cell membrane and within the cytoplasm of PC-3 PCa cells. This probe effectively distinguished PC-3 tumor cells from normal tissues. In a nude mouse model of PCa bone metastasis, 99mTc-DTPA-c(CGRRAGGSC) successfully labeled metastatic PCa cells in the bone, as confirmed by bone-scan positron emission tomography/computed tomography imaging. Compared with 99mTc–methylene diphosphonate (MDP), the probe demonstrated a higher signal-to-noise ratio and exhibited efficient clearance from most nontarget tissues within 24 hours. These findings highlight the promising potential of this molecular probe as a diagnostic imaging agent and a candidate for targeted therapy of PCa bone metastases.

4. The contribution of interleukin-11 to prostate cancer development and progression

Multiple factors contribute to the upregulation of IL-11 expression in PCa cells, subsequently promoting tumor progression through distinct downstream signaling pathways. Intratumoral hypoxia, a defining characteristic of many solid tumors, elicits transcriptional responses that are predominantly mediated by hypoxia-inducible factor 1.[41] Cooperative interactions between hypoxia-inducible factor 1 and activator protein-1 have been shown to induce IL-11 promoter activation in various human cancer cell types, including PCa cells.[42] Elevated IL-11 levels, acting through the p38/STAT1 signaling axis, enhance the clonogenic capacity of PC-3 cells, while having no significant effect on cellular proliferation, apoptosis, or cell cycle progression.[42] Recombinant IL-11 has been demonstrated to enhance the proliferative capacity of the human PCa cell lines LNCaP and PC-3, suppress apoptosis, and promote tumor cell invasiveness and migratory behavior.[43] These effects were further supported by IL-11-induced upregulation of SRY-box transcription factor 2 (SOX2) and cluster of differentiation 44 (CD44), which are markers associated with cancer stemness.[43] Prostate fibroblasts overexpressing the LIM domain only 2 have been shown to secrete IL-11, which in turn activates the androgen receptor in an androgen-independent manner via activation of the STAT3 and ERK/MAPK signaling pathways. This signaling cascade enhances the proliferation, survival, and invasive potential of LNCaP and VCaP cells.[39] Notably, androgen receptor inactivation upregulates LIM domain only 2 expression, suggesting that IL-11 mediates the development of castration resistance in PCa.[39] Overall, IL-11 promotes the malignant behavior of PCa cells, and its activity is modulated by the tumor microenvironment and neighboring cells within the prostate. Constructing a regulatory network for IL-11-mediated PCa progression from the perspective of the tumor microenvironment and intercellular interactions will contribute to a deeper understanding of the role of IL-11 in PCa development and progression.

5. The role of interleukin-11 in prostate cancer bone metastasis

Interleukin-11 receptor alpha is expressed in both osteoblasts and osteoclasts, implying a regulatory role for IL-11 in maintaining the balance between bone formation and bone resorption.[17] Zhang et al.[44] identified binding elements for the transcription factor RUNX2 in the IL-11 promoter. The transcription factor RUNX2 is critically involved in osteolysis and bone metastasis. Notably, the co-expression of RUNX2 and IL-11 was observed exclusively in highly invasive PC3-H cells, whereas their expression was nearly undetectable in less invasive PC3-L and non–bone-metastatic LNCaP cells. The upregulation of IL-11 induced by RUNX2 enhanced the expression of osteolytic genes such as parathyroid hormone-related protein and receptor activator of nuclear factor κB ligand in PCa cells. Therefore, the RUNX2/IL-11 signaling axis may be a potential therapeutic target for preventing PCa bone metastasis.[44] Furthermore, Zhang et al.[45] demonstrated that the acetylation of Krüppel-like factor 5 (KLF5) in PC-3 cells promotes IL-11 secretion through the upregulation of the C-X-C motif chemokine receptor 4 (CXCR4), thereby facilitating osteoclast differentiation and contributing to bone metastasis of PCa cells. In addition to tumor cell proliferation, the bone metastasis of PCa cells is also influenced by the bone microenvironment, where alterations in osteogenesis or osteolysis can release cytokines that promote the metastatic growth of tumor cells.[46] As a bone-regulatory factor,[22] IL-11 may be involved in bone metastasis of PCa by modulating the bone microenvironment, including its effects on osteoblasts and osteoclasts.

6. The influence of interleukin-11 on chemotherapeutic resistance in prostate cancer

Docetaxel (DTX) resistance poses a major challenge in the clinical management of PCa. Emerging evidence indicates that elevated IL-11 expression contributes to the development of DTX resistance in PCa cells. Using a single-cell deconvolution algorithm, Cheng et al.[47] analyzed the cytokine secretion profiles associated with docetaxel resistance in 3 prostate cancer organoid models (MSK-PCa3, MSK-PCa7, and PM154). Their findings revealed that an IL-11/IL-11Rα autocrine signaling loop, functioning through the JAK1/STAT4 pathway, enhanced PCa resistance to DTX by activating c-MYC transcription.[47]

In DU145 and PC-3 PCa cells, acetylated KLF5 activates CXCR4, thereby promoting the transcription and secretion of IL-11. Tumor-derived IL-11 subsequently contributes to the development of DTX resistance in these cells.[45] Conversely, inhibition of the acetylated KLF5/CXCR4 signaling axis not only suppresses IL-11 expression but also restores DTX sensitivity in PCa cells.[45] To date, studies investigating the role of IL-11 in the acquisition of DTX resistance remain limited, and it remains unclear whether IL-11 contributes to resistance to other chemotherapeutic agents in PCa.

7. Therapeutic implications of interleukin-11 in prostate cancer

Pasqualini et al. developed a ligand-directed peptidomimetic drug, termed bone metastasis-targeting peptidomimetic-11 (BMTP-11), which specifically targets IL-11Rα. In a mouse model of PCa, the intravenous administration of BMTP-11 markedly suppressed the growth of both DU145 and LNCaP cells. Following these findings, a phase I clinical trial (NCT00872157) was initiated, which enrolled 6 patients with PCa with confirmed bone metastases.[48] The results demonstrated that BMTP-11 effectively localized to PCa cells within metastatic bone lesions and induced tumor cell apoptosis. Although no BMTP-11-related fatalities were reported during the study period, BMTP-11 at doses ranging from 18 to 36 mg/m2 was associated with reversible acute kidney injury characterized by elevated serum creatinine levels and proteinuria. Notably, 2 patients were unable to complete the full treatment cycle due to renal toxicity.

Sipuleucel-T, an autologous dendritic cell-based vaccine loaded with prostatic acid phosphatase fused to granulocyte-macrophage colony-stimulating factor, remains the only U.S. Food and Drug Administration-approved therapeutic vaccine for PCa.[49] Expanding on this vaccine platform, Mackiewicz et al.[50] developed an IL-11-secreting transgenic mouse adenocarcinoma prostate cell-based vaccine (TRAMP-H11). When administered in combination with low-dose cyclophosphamide, TRAMP-H11 significantly enhanced the generation of CD8 + cytotoxic T cells, CD4 + helper T cells, and memory T cells while concurrently suppressing the production of regulatory T cells. This immunomodulatory effect substantially augmented the antitumor immune response and prolonged median survival in mice with orthotopic prostate tumors (71 vs. 53 days, p = 0.03), exhibiting more favorable efficacy than cyclophosphamide monotherapy (71 vs. 54 days, p = 0.32).[50] Interleukin-11–based therapeutic strategies have shown potential clinical value. However, large-scale clinical studies are required to validate their efficacy and safety in humans.

8. Conclusions

Interleukin-11 has been implicated in promoting tumor initiation, progression, and metastasis in multiple cancer types. Substantial evidence indicates that IL-11 is involved in various stages of PCa pathogenesis, highlighting its potential as a biomarker for early diagnosis and a strategic target for therapeutic intervention. Table 1 summarizes the studies on IL-11 in prostate cancer. Given that IL-11 is a bone metabolic regulator, a thorough elucidation of its underlying mechanisms in PCa bone metastasis will advance the management and treatment of patients with PCa with skeletal involvement.

Table 1.

Summary of studies investigating the role of IL-11 in prostate cancer.

Author Main research focus Clinical relevance Key findings
Campbell et al.[37] Expression of the IL-11/IL-11Rα system in prostate cancer cells and tissues Diagnosis 1. The mRNA and extracellular secretion levels of IL-11 are elevated in prostate cancer cell lines.
2. The protein expression level of IL-11Rα is increased in prostate cancer tissues.
Furuya et al.[38] Differences in serum IL-11 levels among healthy individuals, patients with benign prostatic hyperplasia, and patients with prostate cancer Diagnosis 1. The serum IL-11 level in patients with hormone-refractory prostate cancer is significantly higher than that in patients with untreated prostate cancer.
2. No statistically significant difference in IL-11 levels between patients with prostate cancer and those with benign prostatic hyperplasia.
Chen et al.[39] The role and mechanism of LMO2-overexpressing prostatic fibroblasts in prostate cancer progression Diagnosis
Etiology and pathogenesis
Tumor progression		 1. Serum IL-11 level is higher in patients with metastatic prostate cancer than in patients with benign prostate and localized prostate cancer.
2. Elevated IL-11 levels are associated with higher Gleason scores and PSA levels.
3. IL-11 derived from prostatic fibroblasts enhances proliferation, antiapoptotic capacity, invasiveness, and castration resistance of LNCaP and VCaP cells by inducing the phosphorylation of STAT3, ERK, and AR.
Qinghua et al.[40] Synthesis of the radiolabeled molecular probe 99mTc-DTPA-c(CGRRAGGSC) and its application in the recognition of prostate cancer cells Diagnosis
Targeted therapy		 1. 99mTc-DTPA-c(CGRRAGGSC) can specifically recognize PC-3 cells.
2. Bone-metastatic prostate cancer cells targeted by 99mTc-DTPA-c(CGRRAGGSC) can be detected using PET/CT.
Onnis et al.[42] The role and mechanism of hypoxia-induced IL-11 expression in tumor progression Etiology and pathogenesis IL-11 mediates hypoxia-induced activation of the p38/STAT1 signaling pathway, thereby promoting the growth of PC-3 cells.
Yu et al.[43] Effects of different interleukins on the stemness and biological behavior of prostate cancer cells Tumor progression
Chemotherapy resistance		 Recombinant IL-11 protein enhances the stemness of LNCaP and PC-3 cells, thereby promoting proliferation, invasion, and migration of LNCaP and PC-3 cells, as well as resistance to docetaxel.
Zhang et al.[44] The role and mechanism of RUNX2 and IL-11 in bone metastasis of prostate cancer Bone metastasis RUNX2-induced upregulation of IL-11 increases the expression of the osteolytic genes PTHrP and RANKL in PC-3 cells.
Zhang et al.[45] The role and mechanism of acetylated KLF5 in bone metastasis and docetaxel resistance of prostate cancer Bone metastasis
Chemotherapy resistance		 The Ac-KLF5/CXCR4 axis in prostate cancer cells promotes bone metastasis by inducing osteoclast differentiation through IL-11 paracrine signaling and confers docetaxel resistance to prostate cancer cells.
Cheng et al.[47] The role and mechanism of the IL-11/IL-11R autocrine loop in docetaxel resistance of prostate cancer Chemotherapy resistance In prostate cancer organoid models (MSK-PCa3, MSK-PCa7, and PM154), the IL-11/IL-11Rα autocrine loop enhances docetaxel resistance in prostate cancer through the JAK1/STAT4 pathway.
Pasqualini et al.[48] Safety and therapeutic efficacy of the IL-11R-targeting peptidomimetic drug BMTP-11 in bone-metastatic prostate cancer Targeted therapy Intravenous administration of BMTP-11 effectively inhibits the growth of bone-metastatic prostate cancer cells but may cause reversible acute kidney injury.
Mackiewicz et al.[50] Efficacy of the cell-based vaccine TRAMP-H11 combined with cyclophosphamide in the orthotopic murine prostate cancer model Targeted therapy TRAMP-H11 inhibits the growth of prostatic tumor cells and prolongs the median survival of prostate cancer mice by enhancing antitumor immune responses.
Open in a new tab

AR = androgen receptor; ERK = extracellular signal-regulated kinase; IL-11 = interleukin-11; IL-11Rα = IL-11 receptor alpha; PET/CT = positron emission tomography–computed tomography; PSA = prostate-specific antigen; STAT3 = signal transducer and activator of transcription 3.

Interleukin-11 plays a critical role in the progression of PCa to castration-resistant PCa and in the development of resistance to docetaxel. Therefore, therapeutic strategies targeting IL-11 signaling may improve the clinical outcomes of patients with PCa. Currently, phase I clinical trials evaluating neutralizing antibodies against IL-11 or IL-11Rα are ongoing for various diseases, including pulmonary fibrosis (NCT05331300 and NCT05658107) and solid tumors (NCT05911984). However, further preclinical and clinical investigations are required to establish the safety and efficacy of IL-11/IL-11R neutralizing antibodies for clinical application in PCa.

Acknowledgments

None.

Statement of ethics

Not applicable.

Conflict of interest statement

GZ is an Associate Editor of Current Urology and confirms no involvement in any stage of this article’s review process, ensuring unbiased editorial decision-making. The remaining authors have no conflicts of interest to disclose.

Funding source

This work was financed by grants from the National Natural Science Foundation of China (82270745 and 82270798), the Natural Science Foundation of Guangdong Province (2024A1515012699), and the Science and Technology Plan Project of Guangzhou (202201020416).

Author contributions

JZ: Conceptualization, writing-original draft;XD: Conceptualization, writing-review and editing, funding acquisition;ZW: Writing-original draft;

WZ: Conceptualization, writing-review and editing;ZZ: Funding acquisition, supervision, writing-review and editing;

GZ: Funding acquisition, supervision, writing-review and editing.

Data availability

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Footnotes

J.Z., X.D., and Z.W. contributed to this article equally.

How to cite this article: Zhong J, Duan X, Wei Z, Zhu W, Zhao Z, Zeng G. Interleukin-11: A pivotal player and potential therapeutic target in prostate cancer. Curr Urol 2026;20(3):174–179. doi: 10.1097/CU9.0000000000000323

References

  • [1].Ferlay J, Colombet M, Soerjomataram I, et al. Cancer statistics for the year 2020: An overview. Int J Cancer 2021;149(4):778–789. [DOI] [PubMed] [Google Scholar]
  • [2].Siegel RL, Miller KD, Fuchs HE, Jemal A. Cancer statistics, 2022. CA Cancer J Clin 2022;72(1):7–33. [DOI] [PubMed] [Google Scholar]
  • [3].Siegel RL, Kratzer TB, Giaquinto AN, Sung H, Jemal A. Cancer statistics, 2025. CA Cancer J Clin 2025;75(1):10–45. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [4].Devasia TP, Mariotto AB, Nyame YA, Etzioni R. Estimating the number of men living with metastatic prostate cancer in the United States. Cancer Epidemiol Biomarkers Prev 2023;32(5):659–665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [5].Derouet D, Rousseau F, Alfonsi F, et al. Neuropoietin, a new IL-6-related cytokine signaling through the ciliary neurotrophic factor receptor. Proc Natl Acad Sci U S A 2004;101(14):4827–4832. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [6].Murakami M, Kamimura D, Hirano T. New IL-6 (gp130) family cytokine members, CLC/NNT1/BSF3 and IL-27. Growth Factors 2004;22(2):75–77. [DOI] [PubMed] [Google Scholar]
  • [7].Zhao Q, Qian L, Guo Y, et al. IL11 signaling mediates piR-2158 suppression of cell stemness and angiogenesis in breast cancer. Theranostics 2023;13(7):2337–2349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [8].Tang M, Xu M, Wang J, et al. Brain metastasis from EGFR-mutated non-small cell lung cancer: Secretion of IL11 from astrocytes up-regulates PDL1 and promotes immune escape. Adv Sci (Weinh) 2024;11(26):e2306348. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [9].Calon A, Espinet E, Palomo-Ponce S, et al. Dependency of colorectal cancer on a TGF-β-driven program in stromal cells for metastasis initiation. Cancer Cell 2012;22(5):571–584. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [10].Paul SR, Bennett F, Calvetti JA, et al. Molecular cloning of a cDNA encoding interleukin 11, a stromal cell-derived lymphopoietic and hematopoietic cytokine. Proc Natl Acad Sci U S A 1990;87(19):7512–7516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [11].Yin T, Yasukawa K, Taga T, Kishimoto T, Yang YC. Identification of a 130-kilodalton tyrosine-phosphorylated protein induced by interleukin-11 as JAK2 tyrosine kinase, which associates with gp130 signal transducer. Exp Hematol 1994;22(5):467–472. [PubMed] [Google Scholar]
  • [12].Ernst M, Najdovska M, Grail D, et al. STAT3 and STAT1 mediate IL-11-dependent and inflammation-associated gastric tumorigenesis in gp130 receptor mutant mice. J Clin Invest 2008;118(5):1727–1738. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [13].Putoczki TL, Dobson RCJ, Griffin MDW. The structure of human interleukin-11 reveals receptor-binding site features and structural differences from interleukin-6. Acta Crystallogr D Biol Crystallogr 2014;70(Pt 9):2277–2285. [DOI] [PubMed] [Google Scholar]
  • [14].Van Leuven F, Stas L, Hilliker C, Miyake Y, Bilinski P, Gossler A. Molecular cloning and characterization of the human interleukin-11 receptor alpha-chain gene, IL11RA, located on chromosome 9p13. Genomics 1996;31(1):65–70. [DOI] [PubMed] [Google Scholar]
  • [15].Chérel M, Sorel M, Lebeau B, et al. Molecular cloning of two isoforms of a receptor for the human hematopoietic cytokine interleukin-11. Blood 1995;86(7):2534–2540. [PubMed] [Google Scholar]
  • [16].Elias JA, Zheng T, Einarsson O, et al. Epithelial interleukin-11. Regulation by cytokines, respiratory syncytial virus, and retinoic acid. J Biol Chem 1994;269(35):22261–22268. [PubMed] [Google Scholar]
  • [17].Romas E, Udagawa N, Zhou H, et al. The role of gp130-mediated signals in osteoclast development: Regulation of interleukin 11 production by osteoblasts and distribution of its receptor in bone marrow cultures. J Exp Med 1996;183(6):2581–2591. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [18].Trepicchio WL, Wang L, Bozza M, Dorner AJ. IL-11 regulates macrophage effector function through the inhibition of nuclear factor-kappaB. J Immunol 1997;159(11):5661–5670. [PubMed] [Google Scholar]
  • [19].Grötzinger J, Kernebeck T, Kallen KJ, Rose-John S. IL-6 type cytokine receptor complexes: Hexamer, tetramer or both? Biol Chem 1999;380(7-8):803–813. [DOI] [PubMed] [Google Scholar]
  • [20].Putoczki TL, Ernst M. IL-11 signaling as a therapeutic target for cancer. Immunotherapy 2015;7(4):441–453. [DOI] [PubMed] [Google Scholar]
  • [21].Fiebelkow J, Guendel A, Guendel B, et al. The tyrosine phosphatase SHP2 increases robustness and information transfer within IL-6-induced JAK/STAT signalling. Cell Commun Signal 2021;19(1):94. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [22].Dong B, Zhu J, Chen X, et al. The emerging role of interleukin-(IL)-11/IL-11R in bone metabolism and homeostasis: From cytokine to osteokine. Aging Dis 2023;14(6):2113–2126. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [23].Lokau J, Nitz R, Agthe M, et al. Proteolytic cleavage governs interleukin-11 trans-signaling. Cell Rep 2016;14(7):1761–1773. [DOI] [PubMed] [Google Scholar]
  • [24].Taga T, Hibi M, Hirata Y, et al. Interleukin-6 triggers the association of its receptor with a possible signal transducer, gp130. Cell 1989;58(3):573–581. [DOI] [PubMed] [Google Scholar]
  • [25].Hibi M, Murakami M, Saito M, Hirano T, Taga T, Kishimoto T. Molecular cloning and expression of an IL-6 signal transducer, gp130. Cell 1990;63(6):1149–1157. [DOI] [PubMed] [Google Scholar]
  • [26].van Duijneveldt G, Griffin MDW, Putoczki TL. Emerging roles for the IL-6 family of cytokines in pancreatic cancer. Clin Sci (Lond) 2020;134(16):2091–2115. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [27].Unver N, McAllister F. IL-6 family cytokines: Key inflammatory mediators as biomarkers and potential therapeutic targets. Cytokine Growth Factor Rev 2018;41:10–17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [28].Jones SA, Jenkins BJ. Recent insights into targeting the IL-6 cytokine family in inflammatory diseases and cancer. Nat Rev Immunol 2018;18(12):773–789. [DOI] [PubMed] [Google Scholar]
  • [29].Xu S, Neamati N. gp130: A promising drug target for cancer therapy. Expert Opin Ther Targets 2013;17(11):1303–1328. [DOI] [PubMed] [Google Scholar]
  • [30].Lorenzo J. Cytokines and bone: osteoimmunology. Handb Exp Pharmacol 2020;262:177–230. [DOI] [PubMed] [Google Scholar]
  • [31].Sims NA, Jenkins BJ, Nakamura A, et al. Interleukin-11 receptor signaling is required for normal bone remodeling. J Bone Miner Res 2005;20(7):1093–1102. [DOI] [PubMed] [Google Scholar]
  • [32].Arap W, Kolonin MG, Trepel M, et al. Steps toward mapping the human vasculature by phage display. Nat Med 2002;8(2):121–127. [DOI] [PubMed] [Google Scholar]
  • [33].Zurita AJ, Troncoso P, Cardó-Vila M, Logothetis CJ, Pasqualini R, Arap W. Combinatorial screenings in patients: The interleukin-11 receptor alpha as a candidate target in the progression of human prostate cancer. Cancer Res 2004;64(2):435–439. [DOI] [PubMed] [Google Scholar]
  • [34].Cardó-Vila M, Zurita AJ, Giordano RJ, et al. A ligand peptide motif selected from a cancer patient is a receptor-interacting site within human interleukin-11. PLoS One 2008;3(10):e3452. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [35].Lewis VO, Ozawa MG, Deavers MT, et al. The interleukin-11 receptor alpha as a candidate ligand-directed target in osteosarcoma: Consistent data from cell lines, orthotopic models, and human tumor samples. Cancer Res 2009;69(5):1995–1999. [DOI] [PubMed] [Google Scholar]
  • [36].Maroni P, Bendinelli P, Ferraretto A, Lombardi G. Interleukin 11 (IL-11): Role(s) in breast cancer bone metastases. Biomedicines 2021;9(6):659. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [37].Campbell CL, Jiang Z, Savarese DMF, Savarese TM. Increased expression of the interleukin-11 receptor and evidence of STAT3 activation in prostate carcinoma. Am J Pathol 2001;158(1):25–32. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [38].Furuya Y, Nishio R, Junicho A, Nagakawa O, Fuse H. Serum interleukin-11 in patients with benign prostatic hyperplasia and prostate cancer. Int Urol Nephrol 2005;37(1):69–71. [DOI] [PubMed] [Google Scholar]
  • [39].Chen L, Wang YY, Li D, et al. LMO2 upregulation due to AR deactivation in cancer-associated fibroblasts induces non-cell-autonomous growth of prostate cancer after androgen deprivation. Cancer Lett 2021;503:138–150. [DOI] [PubMed] [Google Scholar]
  • [40].Wu Q, Xu J, Liu L, et al. A radiolabeled nonapeptide probe targeting PC-3 cells and bone metastases of prostate cancer in mice. Contrast Media Mol Imaging 2012;7(2):223–230. [DOI] [PubMed] [Google Scholar]
  • [41].Wang GL, Jiang BH, Rue EA, Semenza GL. Hypoxia-inducible factor 1 is a basic-helix-loop-helix-PAS heterodimer regulated by cellular O2 tension. Proc Natl Acad Sci U S A 1995;92(12):5510–5514. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [42].Onnis B, Fer N, Rapisarda A, Perez VS, Melillo G. Autocrine production of IL-11 mediates tumorigenicity in hypoxic cancer cells. J Clin Invest 2013;123(4):1615–1629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [43].Yu D, Zhong Y, Li X, et al. ILs-3, 6 and 11 increase, but ILs-10 and 24 decrease stemness of human prostate cancer cells in vitro. Oncotarget 2015;6(40):42687–42703. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [44].Zhang X, Wu H, Dobson JR, et al. Expression of the IL-11 gene in metastatic cells is supported by Runx2-Smad and Runx2-cJun complexes induced by TGFβ1. J Cell Biochem 2015;116(9):2098–2108. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [45].Zhang B, Li Y, Wu Q, et al. Acetylation of KLF5 maintains EMT and tumorigenicity to cause chemoresistant bone metastasis in prostate cancer. Nat Commun 2021;12(1):1714. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [46].Croucher PI, McDonald MM, Martin TJ. Bone metastasis: The importance of the neighbourhood. Nat Rev Cancer 2016;16(6):373–386. [DOI] [PubMed] [Google Scholar]
  • [47].Cheng B, Li L, Luo T, et al. Single-cell deconvolution algorithms analysis unveils autocrine IL11-mediated resistance to docetaxel in prostate cancer via activation of the JAK1/STAT4 pathway. J Exp Clin Cancer Res 2024;43(1):67. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [48].Pasqualini R, Millikan RE, Christianson DR, et al. Targeting the interleukin-11 receptor α in metastatic prostate cancer: A first-in-man study. Cancer 2015;121(14):2411–2421. [DOI] [PMC free article] [PubMed] [Google Scholar]
  • [49].Kantoff PW, Higano CS, Shore ND, et al. ; IMPACT Study Investigators. Sipuleucel-T immunotherapy for castration-resistant prostate cancer. N Engl J Med 2010;363(5):411–422. [DOI] [PubMed] [Google Scholar]
  • [50].Mackiewicz J, Kotlarski M, Dondajewska E, Nowicka-Kotlarska A, Krokowicz L, Kazimierczak U. Cell-based hyper-interleukin 6 or hyper-interleukin 11 secreting vaccines combined with low dose cyclophosphamide in an orthotopic murine prostate cancer model. Contemp Oncol (Pozn) 2015;19(3):187–194. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Data Availability Statement

Data sharing is not applicable to this article as no datasets were generated or analyzed during the current study.

Articles from Current Urology are provided here courtesy of Wolters Kluwer Health

RESOURCES