A paracrine circuit in the regulation of the proliferation of macrophages infiltrating murine sarcomas.
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.
Bottazzi
B
B
Istituto di Richerche Farmacologiche Mario Negri, Milano, Italy.
Erba
E
E
Nobili
N
N
Fazioli
F
F
Rambaldi
A
A
Mantovani
A
A
D000818:Animals; D002453:Cell Cycle; D003115:Colony-Stimulating Factors / Q000235:genetics / Q000494:pharmacology; D015870:Gene Expression; D016173:Macrophage Colony-Stimulating Factor; D008264:Macrophages / Q000166:cytology / Q000276:immunology*; D051379:Mice; D010529:Peritoneal Cavity / Q000166:cytology; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D016186:Receptor, Macrophage Colony-Stimulating Factor; D012513:Sarcoma, Experimental / Q000276:immunology* / Q000473:pathology
D003115:Colony-Stimulating Factors; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor