Bottazzi B, Erba E, Nobili N, Fazioli F, Rambaldi A, Mantovani A
Istituto di Richerche Farmacologiche Mario Negri, Milano, Italy.
J Immunol. 1990 Mar 15;144(6):2409-12.
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.
从两种小鼠肉瘤（mFS6和MN/MCA1）中分离出的肿瘤相关巨噬细胞（TAM）与腹膜巨噬细胞（处于S期的细胞占1%至2%）相比，具有较高的增殖活性（处于S期的细胞占7%至11%）。为了阐明导致TAM增殖活性的机制，研究了TAM和肉瘤细胞中c-fms和巨噬细胞（M）-CSF的表达。TAM具有高水平的c-fms原癌基因mRNA转录本，该基因编码一种可能与M-CSF受体相同的酪氨酸激酶，但不表达M-CSF转录本，而肉瘤细胞具有高水平的M-CSF mRNA。肉瘤细胞条件培养基对骨髓细胞具有M-CSF活性，并诱导腹膜渗出液和骨髓来源的巨噬细胞增殖。这些活性被抗M-CSF抗体阻断。这些发现勾勒出了一条调节TAM增殖的旁分泌回路，涉及由肉瘤细胞分泌并作用于表达c-fms的TAM的M-CSF。由于来自这些小鼠肉瘤的TAM具有促进肿瘤生长的活性，在这些肿瘤的巨噬细胞和肿瘤细胞之间可能会发生“乒乓”式的相互滋养相互作用。
