Abstract
Purpose and method: Monocyte chemotactic protein-1 (MCP-1) is a chemokine involved in the macrophage infiltration of tumor tissue. Tumor-associated macrophages (TAMs) are a population of mononuclear phagocytic cells that can have a complex function in tumor biology. The aim of this study was to determine the possible correlation between parenchymal MCP-1 expression and TAM level by immunohistochemical analysis of 97 invasive ductal breast carcinomas, not otherwise specified (NOS), and to investigate their relation with tumor size, histological grade, mitotic activity index (MAI) and lymph node status. Secondly, the MCP-1 mRNA was determined by reverse transcriptase–polymerase chain reaction (RT-PCR) in eight samples of normal breast tissue and 27 samples of invasive breast carcinomas and compared with TAMs. Results: MCP-1 immunoreactivity was present in tumor cells (17/97), but also in TAMs, fibroblasts and endothelial cells. The statistical analysis did not show a significant correlation between MCP-1 expression in tumoral epithelium and tumor size, histological grade, MAI, lymph node status or TAMs. The results of RT-PCR showed that, in all cases of breast carcinomas (27/27) and the majority of normal breast tissues (7/8), the number of detected MCP-1 cDNA copies was above the detection limit. However, carcinomas showed higher levels of MCP-1 mRNA than normal breast tissue. Nevertheless, the statistical analysis did not find a significant correlation between MCP-1 expression and macrophage infiltrations. Conclusion: These results indicate that MCP-1 is probably not the only and/or crucial factor involved in macrophage attraction to tumor locus in breast carcinoma.
Similar content being viewed by others
References
Bingle L, Brown NJ, Lewis CE (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–256
Botazzi B, Polentarutti N, Acero R, Balsari A, Boraschi P, Ghezzi P, et al (1983) Regulation of the macrophage content of neoplasms by chemoattractants. Science 220:210–212
Elston CW, Ellis IO (1991) Pathological prognostic factors in breast carcinoma. The value of histological grade in breast cancer. Experience from a large study with long-term follow-up. Histopathology 19:403–410
Evans R (1972) Macrophages in syngenic animal tumours. Transplantation 14:468–473
Goede V, Brogelli L, Ziche M, Augustin HG (1999) Induction of inflammatory angiogenesis by monocyte chemoattractant protein-1. Int J Cancer 82:756–770
Graves DT, Jiang YL, Williamson A, Valente AJ (1989) Identification of monocyte chemotactic activity produced by malignant cells. Science 245:1490–1492
Graves DT, Barnhill R, Galanopoulos T, Antoniades HN (1992) Expression of monocyte chemotactic protein-1 in human melanoma in vivo. Am J Pathol 140:9–14
Hanada T, Nakagawa M, Emoto A, Nomura T, Nasu N, Nomura Y (2000) Prognostic value of tumor-associated macrophage count in human bladder cancer. Int J Urol 7:263–269
Hayashida K, Nanki T, Girschich H, Yavuz S, Oshi T, Lipsky PE (2001) Synovial stromal cells from rheumatoid arthritis patients attract monocytes by producing MCP-1 and IL-8. Arthritis Res 3:118–126
Hefler L, Tempfer C, Heinze G, Mayerhofer K, Breitnech G, Leodolter S, et al (1999) Monocyte chemoattractant protein-1 serum levels in ovarian cancer patients. Br J Cancer 81:855–859
Inadera H, Egashira K, Takemoto M, Ouchi Y, Matsushima K (1999) Increase in circulating levels of monocyte chemoattractant protein-1 with aging. J Interferon Cytokine Res 19:1179–1182
Jonjić N, Valković T, Lučin K, Iternička Z, Krstulja M, Mustać E, et al (1998) Comparison of microvessel density with tumor associated macrophages in invasive breast carcinoma. Anticancer Res 18:3767–3770
Kraemer R (2000) Regulation of cell migration in atherosclerosis. Curr Atheroscler Rep 2:445–452
Lorenzet R, Peri G, Locati D, Allavena P, Colucci M, Semeraro N, et al (1983) Generation of procoagulant activity by mononuclear phagocytes: a possible mechanism contributing to blood clotting activation within malignant tissues. Blood 62:271–273
Mackay CR (2001) Chemokines: immunology’s high impact factors. Nat Immunol 2:95–101
Mantovani A, Ming WJ, Balotta C, Abdeljalil B, Botazzi B (1986) Origin and regulation of tumor-associated macrophages: the role of tumor-derived chemotactic factors. Biochem Biophys Acta 865:59–67
Mussoni L, Riganti M, Acero R, Erroi A, Conforti G, Mantovani A, et al (1988) Macrophages associated with murine tumours express plasminogen activator activity. Int J Cancer 41:227–230
Negus RP, Stamp GW, Relf MG, Burke F, Malik ST, Bernasconi S, et al (1995) The detection and localization of monocyte chemoattractant protein-1 (MCP-1) in human ovarian cancer. J Clin Invest 95:2391–2396
Nomura S, Shouzu A, Omoto S, Nishikawa M, Fukuhara S (2000) Significance of chemokines and activated platelets in patients with diabetes. Clin Exp Immunol 121:437–444
Peri G, Milanes C, Matteucci C, Ruco L, Zhou D, Sozzani S, et al (1994) A new monoclonal antibody (5D3-F7) which recognizes human monocyte-chemotactic protein-1 but not related chemokines. Development of a sandwich ELISA and in situ detection of producing cells. J Immunol Methods 174:249–257
Polverini PJ, Laibovich SJ (1984) Induction of neovascularisation in vivo and endothelial proliferation in vitro by tumor associated macrophages. Lab Invest 51:635–642
Pyke C, Gream N, Ralfkiaer E, Ronne E, Hoyer Hansen G, Brunner N, et al (1993a) Receptor for urokinase is present in tumor-associated macrophages in ductal breast carcinoma. Cancer Res 53:1911–1915
Pyke C, Ralfkiaer E, Tryggvason K, Dano K (1993b) Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. Am J Pathol 142:359–365
Sato K, Kuratsu JI, Takeshima H, Yoshimura T, Ushio Y (1995) Expression of monocyte chemoattractant protein-1 in meningioma. J Neurosurg 82:874–878
Takeshima H, Kuratsu J, Takeya M, Yoshimura T, Ushio Y (1994) Expression and localization of messenger RNA and protein for monocyte chemoattractant protein-1 in human malignant glioma. J Neurosurg 80:1056–1062
Ueono T, Toi M, Saji H, Muta M, Bando H, Kuroi K, et al (2000) Significance of macrophage chemoattractant protein-1 in macrophage recruitment, angiogenesis and survival in human breast cancer. Clin Cancer Res 6:3282–3289
Valković T, Lučin K, Krstulja M, Dobi-Babić R, Jonjić N (1998) Expression of monocyte chemotactic protein-1 in human invasive ductal breast carcinoma. Pathol Res Pract 194:335–340
Valković T, Dobrila F, Melato M, Sasso F, Jonjić N (2002) Correlation between vascular endothelial growth factor, angiogenesis and tumor associated macrophages in invasive ductal breast carcinoma. Virchows Arch 440:583–588
Wu S, Boyer CM, Whitaker RS, Berchuch A, Wienberg JB, Bast RCJ (1993) Tumor necrosis factor-alpha as an autocrine and paracrine growth factor for ovarian cancer: monokine induction of tumor cell proliferation and tumor necrosis factor-alpha expression. Cancer Res 53:1939–1944
Zeigler-Heitbrock HEL, Theil C, Haas JG, Moller A, Reith A, Muller G (1988) Tumor necrosis factor in human monocyte-mediated antitumor cytotoxicity. Nat Immun Cell Growth Regul 7:280–286
Acknowledgement
This work was supported by the Ministry of Science, Education and Sports of the Republic of Croatia (grant 0062060).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Valković, T., Fučkar, D., Štifter, S. et al. Macrophage level is not affected by monocyte chemotactic protein-1 in invasive ductal breast carcinoma. J Cancer Res Clin Oncol 131, 453–458 (2005). https://doi.org/10.1007/s00432-004-0667-3
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00432-004-0667-3