Skip to main content
NCBI home page
The American Journal of Pathology logoLink to The American Journal of Pathology
. 1996 Aug;149(2):501–509.

Monocyte chemoattractant protein-1 gene expression in prostatic hyperplasia and prostate adenocarcinoma.

L Mazzucchelli 1, P Loetscher 1, A Kappeler 1, M Uguccioni 1, M Baggiolini 1, J A Laissue 1, C Mueller 1
PMCID: PMC1865321  PMID: 8701989

Abstract

Human monocyte chemoattractant protein-1 (MCP-1) has been shown to act as a chemokine in the recruitment of monocyte/macrophages during inflammation states. Furthermore, there is increasing evidence that MCP-1 is involved in the recruitment of tumor-associated macrophages. In vivo, one of the major cellular sources of MCP-1 are the smooth muscle cells. As MCP-1 gene expression and/or protein production in these cells is not necessarily correlated with the accumulation of inflammatory cells, there might possibly be additional functions of this cytokine. In the present study, we investigated by use of 35S-labeled antisense RNA probes whether the MCP-1 gene is expressed in tissue specimens of benign prostatic hyperplasia (n = 13) and specimens of prostate carcinoma (n = 8), both of which are characterized by a prominent fibromuscular stroma and inconspicuous inflammatory infiltrates. MCP-1 transcripts were located in stromal smooth muscle cells and, additionally, in basal cells of benign prostatic glands. In prostate carcinoma, the number of MCP-1 mRNA-expressing cells was significantly less than in benign prostatic hyperplasia. MCP-1 transcripts were located in preserved fibromuscular stroma and in basal cells of entrapped non-neoplastic glands but not in carcinomatous cells. Immunohistochemical staining with polyclonal antibodies raised against MCP-1 revealed strong reactivity in the fibromuscular stroma surrounding both benign and malignant glands. MCP-1 gene expression or immunoreactivity for anti-MCP-1 antibodies was not related to the rare, lymphocytic interstitial infiltrates. The results show that 1) in the absence of significant leukocyte accumulation, it is unlikely that MCP-1 exerts chemotactic functions in the prostate and 2) that MCP-1, in contrast to previous findings in a wide variety of other human neoplasms, is not expressed in carcinomatous cells of the prostate.

Full text

PDF
501

Images in this article

504Figure 2
on p.504
505Figure 3
on p.505
506Figure 4
on p.506

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Albelda S. M. Role of integrins and other cell adhesion molecules in tumor progression and metastasis. Lab Invest. 1993 Jan;68(1):4–17. [PubMed] [Google Scholar]
  2. Antoniades H. N., Neville-Golden J., Galanopoulos T., Kradin R. L., Valente A. J., Graves D. T. Expression of monocyte chemoattractant protein 1 mRNA in human idiopathic pulmonary fibrosis. Proc Natl Acad Sci U S A. 1992 Jun 15;89(12):5371–5375. doi: 10.1073/pnas.89.12.5371. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Baggiolini M., Dewald B., Moser B. Interleukin-8 and related chemotactic cytokines--CXC and CC chemokines. Adv Immunol. 1994;55:97–179. [PubMed] [Google Scholar]
  4. Carr M. W., Roth S. J., Luther E., Rose S. S., Springer T. A. Monocyte chemoattractant protein 1 acts as a T-lymphocyte chemoattractant. Proc Natl Acad Sci U S A. 1994 Apr 26;91(9):3652–3656. doi: 10.1073/pnas.91.9.3652. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Cushing S. D., Berliner J. A., Valente A. J., Territo M. C., Navab M., Parhami F., Gerrity R., Schwartz C. J., Fogelman A. M. Minimally modified low density lipoprotein induces monocyte chemotactic protein 1 in human endothelial cells and smooth muscle cells. Proc Natl Acad Sci U S A. 1990 Jul;87(13):5134–5138. doi: 10.1073/pnas.87.13.5134. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Desbaillets I., Tada M., de Tribolet N., Diserens A. C., Hamou M. F., Van Meir E. G. Human astrocytomas and glioblastomas express monocyte chemoattractant protein-1 (MCP-1) in vivo and in vitro. Int J Cancer. 1994 Jul 15;58(2):240–247. doi: 10.1002/ijc.2910580216. [DOI] [PubMed] [Google Scholar]
  7. Furutani Y., Nomura H., Notake M., Oyamada Y., Fukui T., Yamada M., Larsen C. G., Oppenheim J. J., Matsushima K. Cloning and sequencing of the cDNA for human monocyte chemotactic and activating factor (MCAF). Biochem Biophys Res Commun. 1989 Feb 28;159(1):249–255. doi: 10.1016/0006-291x(89)92430-3. [DOI] [PubMed] [Google Scholar]
  8. Gillitzer R., Wolff K., Tong D., Müller C., Yoshimura T., Hartmann A. A., Stingl G., Berger R. MCP-1 mRNA expression in basal keratinocytes of psoriatic lesions. J Invest Dermatol. 1993 Aug;101(2):127–131. doi: 10.1111/1523-1747.ep12363613. [DOI] [PubMed] [Google Scholar]
  9. Graves D. T., Barnhill R., Galanopoulos T., Antoniades H. N. Expression of monocyte chemotactic protein-1 in human melanoma in vivo. Am J Pathol. 1992 Jan;140(1):9–14. [PMC free article] [PubMed] [Google Scholar]
  10. Graves D. T., Jiang Y. L., Williamson M. J., Valente A. J. Identification of monocyte chemotactic activity produced by malignant cells. Science. 1989 Sep 29;245(4925):1490–1493. doi: 10.1126/science.2781291. [DOI] [PubMed] [Google Scholar]
  11. Hsu S. M., Raine L., Fanger H. Use of avidin-biotin-peroxidase complex (ABC) in immunoperoxidase techniques: a comparison between ABC and unlabeled antibody (PAP) procedures. J Histochem Cytochem. 1981 Apr;29(4):577–580. doi: 10.1177/29.4.6166661. [DOI] [PubMed] [Google Scholar]
  12. Jiang Y., Beller D. I., Frendl G., Graves D. T. Monocyte chemoattractant protein-1 regulates adhesion molecule expression and cytokine production in human monocytes. J Immunol. 1992 Apr 15;148(8):2423–2428. [PubMed] [Google Scholar]
  13. Kleinerman D. I., Troncoso P., Lin S. H., Pisters L. L., Sherwood E. R., Brooks T., von Eschenbach A. C., Hsieh J. T. Consistent expression of an epithelial cell adhesion molecule (C-CAM) during human prostate development and loss of expression in prostate cancer: implication as a tumor suppressor. Cancer Res. 1995 Mar 15;55(6):1215–1220. [PubMed] [Google Scholar]
  14. Knox J. D., Cress A. E., Clark V., Manriquez L., Affinito K. S., Dalkin B. L., Nagle R. B. Differential expression of extracellular matrix molecules and the alpha 6-integrins in the normal and neoplastic prostate. Am J Pathol. 1994 Jul;145(1):167–174. [PMC free article] [PubMed] [Google Scholar]
  15. Koch A. E., Kunkel S. L., Harlow L. A., Johnson B., Evanoff H. L., Haines G. K., Burdick M. D., Pope R. M., Strieter R. M. Enhanced production of monocyte chemoattractant protein-1 in rheumatoid arthritis. J Clin Invest. 1992 Sep;90(3):772–779. doi: 10.1172/JCI115950. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Koch A. E., Kunkel S. L., Pearce W. H., Shah M. R., Parikh D., Evanoff H. L., Haines G. K., Burdick M. D., Strieter R. M. Enhanced production of the chemotactic cytokines interleukin-8 and monocyte chemoattractant protein-1 in human abdominal aortic aneurysms. Am J Pathol. 1993 May;142(5):1423–1431. [PMC free article] [PubMed] [Google Scholar]
  17. Loetscher P., Dewald B., Baggiolini M., Seitz M. Monocyte chemoattractant protein 1 and interleukin 8 production by rheumatoid synoviocytes. Effects of anti-rheumatic drugs. Cytokine. 1994 Mar;6(2):162–170. doi: 10.1016/1043-4666(94)90038-8. [DOI] [PubMed] [Google Scholar]
  18. Loetscher P., Seitz M., Clark-Lewis I., Baggiolini M., Moser B. Monocyte chemotactic proteins MCP-1, MCP-2, and MCP-3 are major attractants for human CD4+ and CD8+ T lymphocytes. FASEB J. 1994 Oct;8(13):1055–1060. doi: 10.1096/fasebj.8.13.7926371. [DOI] [PubMed] [Google Scholar]
  19. Mantovani A. Tumor-associated macrophages in neoplastic progression: a paradigm for the in vivo function of chemokines. Lab Invest. 1994 Jul;71(1):5–16. [PubMed] [Google Scholar]
  20. Matsushima K., Larsen C. G., DuBois G. C., Oppenheim J. J. Purification and characterization of a novel monocyte chemotactic and activating factor produced by a human myelomonocytic cell line. J Exp Med. 1989 Apr 1;169(4):1485–1490. doi: 10.1084/jem.169.4.1485. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Mazzucchelli L., Hauser C., Zgraggen K., Wagner H. E., Hess M. W., Laissue J. A., Mueller C. Differential in situ expression of the genes encoding the chemokines MCP-1 and RANTES in human inflammatory bowel disease. J Pathol. 1996 Feb;178(2):201–206. doi: 10.1002/(SICI)1096-9896(199602)178:2<201::AID-PATH440>3.0.CO;2-4. [DOI] [PubMed] [Google Scholar]
  22. Mazzucchelli L., Hauser C., Zgraggen K., Wagner H., Hess M., Laissue J. A., Mueller C. Expression of interleukin-8 gene in inflammatory bowel disease is related to the histological grade of active inflammation. Am J Pathol. 1994 May;144(5):997–1007. [PMC free article] [PubMed] [Google Scholar]
  23. Miller M. D., Krangel M. S. Biology and biochemistry of the chemokines: a family of chemotactic and inflammatory cytokines. Crit Rev Immunol. 1992;12(1-2):17–46. [PubMed] [Google Scholar]
  24. Minty A., Chalon P., Guillemot J. C., Kaghad M., Liauzun P., Magazin M., Miloux B., Minty C., Ramond P., Vita N. Molecular cloning of the MCP-3 chemokine gene and regulation of its expression. Eur Cytokine Netw. 1993 Mar-Apr;4(2):99–110. [PubMed] [Google Scholar]
  25. Mueller C., Gershenfeld H. K., Lobe C. G., Okada C. Y., Bleackley R. C., Weissman I. L. A high proportion of T lymphocytes that infiltrate H-2-incompatible heart allografts in vivo express genes encoding cytotoxic cell-specific serine proteases, but do not express the MEL-14-defined lymph node homing receptor. J Exp Med. 1988 Mar 1;167(3):1124–1136. doi: 10.1084/jem.167.3.1124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Navab M., Imes S. S., Hama S. Y., Hough G. P., Ross L. A., Bork R. W., Valente A. J., Berliner J. A., Drinkwater D. C., Laks H. Monocyte transmigration induced by modification of low density lipoprotein in cocultures of human aortic wall cells is due to induction of monocyte chemotactic protein 1 synthesis and is abolished by high density lipoprotein. J Clin Invest. 1991 Dec;88(6):2039–2046. doi: 10.1172/JCI115532. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Reinecker H. C., Loh E. Y., Ringler D. J., Mehta A., Rombeau J. L., MacDermott R. P. Monocyte-chemoattractant protein 1 gene expression in intestinal epithelial cells and inflammatory bowel disease mucosa. Gastroenterology. 1995 Jan;108(1):40–50. doi: 10.1016/0016-5085(95)90006-3. [DOI] [PubMed] [Google Scholar]
  28. Rollins B. J., Sunday M. E. Suppression of tumor formation in vivo by expression of the JE gene in malignant cells. Mol Cell Biol. 1991 Jun;11(6):3125–3131. doi: 10.1128/mcb.11.6.3125. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Schall T. J., Jongstra J., Dyer B. J., Jorgensen J., Clayberger C., Davis M. M., Krensky A. M. A human T cell-specific molecule is a member of a new gene family. J Immunol. 1988 Aug 1;141(3):1018–1025. [PubMed] [Google Scholar]
  30. Taub D. D., Proost P., Murphy W. J., Anver M., Longo D. L., van Damme J., Oppenheim J. J. Monocyte chemotactic protein-1 (MCP-1), -2, and -3 are chemotactic for human T lymphocytes. J Clin Invest. 1995 Mar;95(3):1370–1376. doi: 10.1172/JCI117788. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Tonetti M. S., Imboden M. A., Gerber L., Lang N. P., Laissue J., Mueller C. Localized expression of mRNA for phagocyte-specific chemotactic cytokines in human periodontal infections. Infect Immun. 1994 Sep;62(9):4005–4014. doi: 10.1128/iai.62.9.4005-4014.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Van Damme J., Proost P., Lenaerts J. P., Opdenakker G. Structural and functional identification of two human, tumor-derived monocyte chemotactic proteins (MCP-2 and MCP-3) belonging to the chemokine family. J Exp Med. 1992 Jul 1;176(1):59–65. doi: 10.1084/jem.176.1.59. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Ware J. L. Prostate cancer progression. Implications of histopathology. Am J Pathol. 1994 Nov;145(5):983–993. [PMC free article] [PubMed] [Google Scholar]
  34. Yamashiro S., Takeya M., Nishi T., Kuratsu J., Yoshimura T., Ushio Y., Takahashi K. Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors. Am J Pathol. 1994 Oct;145(4):856–867. [PMC free article] [PubMed] [Google Scholar]
  35. Yoshimura T., Leonard E. J. Human monocyte chemoattractant protein-1: structure and function. Cytokines. 1992;4:131–152. [PubMed] [Google Scholar]
  36. Yoshimura T., Robinson E. A., Tanaka S., Appella E., Kuratsu J., Leonard E. J. Purification and amino acid analysis of two human glioma-derived monocyte chemoattractants. J Exp Med. 1989 Apr 1;169(4):1449–1459. doi: 10.1084/jem.169.4.1449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Yoshimura T., Robinson E. A., Tanaka S., Appella E., Leonard E. J. Purification and amino acid analysis of two human monocyte chemoattractants produced by phytohemagglutinin-stimulated human blood mononuclear leukocytes. J Immunol. 1989 Mar 15;142(6):1956–1962. [PubMed] [Google Scholar]
  38. Yoshimura T., Yuhki N., Moore S. K., Appella E., Lerman M. I., Leonard E. J. Human monocyte chemoattractant protein-1 (MCP-1). Full-length cDNA cloning, expression in mitogen-stimulated blood mononuclear leukocytes, and sequence similarity to mouse competence gene JE. FEBS Lett. 1989 Feb 27;244(2):487–493. doi: 10.1016/0014-5793(89)80590-3. [DOI] [PubMed] [Google Scholar]
  39. Yu X., Barnhill R. L., Graves D. T. Expression of monocyte chemoattractant protein-1 in delayed type hypersensitivity reactions in the skin. Lab Invest. 1994 Aug;71(2):226–235. [PubMed] [Google Scholar]

Articles from The American Journal of Pathology are provided here courtesy of American Society for Investigative Pathology

RESOURCES