TABLE 5.
Mechanisms of antitumor drug resistance mediated by MSCs.
| Tumor type | Drug resistance | Mechanisms | References |
| ALL | Cytarabine, etoposide | T-ALL cell/MSC adhesion mediating mitochondria transferring. | Wang J. et al., 2018 |
| Vincristine | MSCs secreting CXCL12, binding to surface CXCR4 on ALL cells, mediating apoptosis rate, and apoptosis-related protein expression. | Wang S. et al., 2020 | |
| Breast cancer | Platinum | MSCs secreting two unique PIFAs. | Roodhart et al., 2011 |
| Carboplatin | MSCs releasing exosomes containing miR-222/223. | Bliss et al., 2016 | |
| Cisplatin | MSCs-derived IL-6 activating STAT3 pathway with the markedly decreasing expression of Bax. | Xu et al., 2018 | |
| CML | Imatinib | MSCs secreting CXCL12, reducing activation of caspase-3 and promoting the expression of Bcl-XL. | Vianello et al., 2010 |
| TKI | MSCs increasing N-Cadherin-mediated adhesion and enhancing transcription of β-catenin target genes in primary CML CD34+ cells. | Zhang et al., 2013 | |
| TKI | MSCs releasing IL-7, mediating JAK1/STAT5 pathway, activating bypassed BCR/ABL signals. | Zhang et al., 2019 | |
| Gastric cancer | 5-FU | MSC-exosomes activating CaM-Ks, triggering downstream Raf/MEK/ERK signaling cascade activation. | Ji et al., 2015 |
| 5-FU, oxaliplatin | MSCs secreting TGF-β1, promoting FAO to support stemness features and drug resistance. | He et al., 2019 | |
| 5-FU, oxaliplatin | MSC-induced lncRNA HCP5 driving FAO through miR-3619-5p/AMPK/PGC1α/CEBPB axis. | Wu et al., 2020 | |
| HCC | Cisplatin | The overexpression of TGF-β in MSCs promoting autophagy. | Han et al., 2014 |
| Multiple myeloma | Bortezomib | MSC-exosomes activating several pathways including p38, p53, c-Jun N-terminal kinase, and AKT pathways related to survival. | Wang et al., 2014 |
| NPC | Cisplatin | MSC-derived IL-6 upregulating STAT3 signal pathway, increasing expression of CD73. | Zeng et al., 2020 |
| Osteosarcoma | Doxorubicin | MSC-derived IL-6 activating the JAK2/STAT3 signaling, with the subsequent up-regulation of MRP and P-gP expression. | Tu et al., 2016 |
| Ovarian cancer | Carboplatin | MSCs highly releasing CXCL1/2 and IL-8, promoting M2 macrophages differentiation. | Le Naour et al., 2020 |
| HNSCC | Paclitaxel | MSCs secreting various cytokines in a paracrine manner. | Scherzed et al., 2011 |
MSCs, mesenchymal stem cells; ALL, acute lymphoblastic leukemia; PIFAs, platinum-induced fatty acids; CML, chronic myeloid leukemia; TKI, tyrosine kinase inhibitors; 5-FU, 5-fluorouracil; FAO, fatty acid oxidation; lncRNA, long non-coding RNA; HCC, hepatocellular carcinoma; NPC, nasopharyngeal carcinoma; MRP, multidrug resistance protein; P-gp, p-glycoprotein; HNSCC, head and neck squamous cell carcinoma.