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Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors.

Abstract
By immunohistochemistry using anti-rat macrophage monoclonal antibodies RM-1, ED1, ED2, ED3, TRPM-3, and Ki-M2R, we studied transplanted rat tumors of 9L (rat gliosarcoma), Ad-2 (rat mammary carcinoma), and MT-P (rat malignant fibrous histiocytoma) cell lines to examine the distribution pattern of macrophages within and around the tumors. Most tumor-associated macrophages expressed RM-1, ED1, and Ia antigens, indicating activated macrophages. Based on differences in their immunophenotypical expression, these macrophages were distinguished into two major subpopulations. One expressed TRPM-3 and/or ED3, and the other was positive for ED2 and Ki-M2R. The former was considered to be monocyte-derived macrophages, whereas the latter showed the immunophenotype of tissue-fixed, resident macrophages. Infiltration and distribution patterns in the two macrophage subpopulations differed in the three different tumors. Monocyte-derived, activated macrophages infiltrated into 9L- and Ad-2-transplanted tumors, which markedly produced monocyte chemoattractant protein-1 (MCP-1). Additionally, numerous ED2- and Ki-M2R-positive macrophages were observed within the Ad-2-transplanted tumors, and some of them expressed TRPM-3. However, there were few macrophages in the MT-P-transplanted tumors that showed no MCP-1 production. In transplanted tumors of four MT-P/MCP-1 cell lines established by transfecting a rat MCP-1 gene expression vector (pCEP4/MCP-1) into the MT-P cell line, different levels of MCP-1 production were detected, which correlated well with the numbers of intratumorally infiltrated TRPM-3-positive macrophages. In contrast, ED2- and Ki-M2R-positive macrophages were not detected in any MT-P/MCP-1-transplanted tumors. MT-P/MCP-1-transplanted tumors exhibited lower growth rate than parental MT-P-transplanted tumors. These results indicate that tumor-derived MCP-1 induces intratumoral infiltration of monocyte-derived macrophages, but not macrophages with the immunophenotype of tissue-fixed, resident type. The former population of macrophages seems to have a suppressive effect on the growth of tumors.
AuthorsS Yamashiro, M Takeya, T Nishi, J Kuratsu, T Yoshimura, Y Ushio, K Takahashi
JournalThe American journal of pathology (Am J Pathol) Vol. 145 Issue 4 Pg. 856-67 (Oct 1994) ISSN: 0002-9440 [Print] United States
PMID7943176 (Publication Type: Journal Article)
Chemical References
  • Chemokine CCL2
  • Chemotactic Factors
Topics
  • Animals
  • Cell Line, Transformed
  • Chemokine CCL2
  • Chemotactic Factors (genetics, pharmacology)
  • Gene Expression
  • Genetic Vectors
  • Immunohistochemistry
  • Immunophenotyping
  • Macrophages (classification, physiology)
  • Male
  • Monocytes (cytology)
  • Neoplasm Transplantation
  • Neoplasms, Experimental (pathology)
  • Rats
  • Rats, Inbred F344
  • Rats, Inbred Strains
  • Transfection

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