A paracrine circuit in the regulation of the proliferation of macrophages infiltrating murine sarcomas

Barbara Bottazzi, Eugenio Erba, Nadia Nobili, Francesca Fazioli, Alessandro Rambaldi, Alberto Mantovani

Research output: Contribution to journalArticlepeer-review

Abstract

Tumor-associated macrophages (TAM) isolated from two murine sarcomas (mFS6 and MN/MCA1) had high levels of proliferative activity (7 to 11% of cells in S phase) compared to peritoneal macrophages (1 to 2% of cells in S phase). In an effort to elucidate the mechanisms responsible for the proliferative activity of TAM, expression of c-fms and macrophage (M)-CSF was investigated in TAM and sarcoma cells. TAM had high levels of mRNA transcripts of the c-fms protooncogene, which encodes a tyrosine kinase probably identical to the M-CSF receptor, but did not express M-CSF transcripts whereas sarcoma cells had high levels of M-CSF mRNA. Sarcoma cell conditioned medium had M-CSF activity on bone marrow cells and induced proliferation of peritoneal exudate and bone marrow-derived macrophages. These activities were blocked by anti-M-CSF antibodies. These findings outline a paracrine circuit in the regulation of TAM proliferation, involving M-CSF, secreted by sarcoma cells and acting on c-fms expressing TAM. Inasmuch as TAM from these murine sarcomas have tumor growth promoting activity, a "ping pong" reciprocal feeding interaction may occur between macrophages and neoplastic cells in these tumors.

Original languageEnglish
Pages (from-to)2409-2412
Number of pages4
JournalJournal of Immunology
Volume144
Issue number6
Publication statusPublished - Mar 15 1990

ASJC Scopus subject areas

  • Immunology

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