Tumor-derived monocyte chemoattractant protein-1 induces intratumoral infiltration of monocyte-derived macrophage subpopulation in transplanted rat tumors.
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.
Yamashiro
S
S
Second Department of Pathology, Kumamoto University School of Medicine, Japan.
Takeya
M
M
Nishi
T
T
Kuratsu
J
J
Yoshimura
T
T
Ushio
Y
Y
Takahashi
K
K
D000818:Animals; D002461:Cell Line, Transformed; D018932:Chemokine CCL2; D002630:Chemotactic Factors / Q000235:genetics / Q000494:pharmacology*; D015870:Gene Expression; D005822:Genetic Vectors; D007150:Immunohistochemistry; D016130:Immunophenotyping; D008264:Macrophages / Q000145:classification / Q000502:physiology*; D008297:Male; D009000:Monocytes / Q000166:cytology; D009368:Neoplasm Transplantation; D009374:Neoplasms, Experimental / Q000473:pathology*; D051381:Rats; D011916:Rats, Inbred F344; D011919:Rats, Inbred Strains; D014162:Transfection
D018932:Chemokine CCL2; D002630:Chemotactic Factors