Osteopetrotic CSF-1(op) (op/op) mice that have a CSF-1 gene defect and a profound macrophage deficiency (36) have been used as a model to examine tumor growth. These mice show an impaired tumor development (Lewis lung carcinoma) when compared to normal littermates, which is reversed by CSF-1 treatment (37). Crossing CSF-1(op) mice with a transgenic mouse susceptible to mammary cancer prevented macrophage accumulation in mammary tumors. In the macrophage-deficient mice, the incidence and initial rates of growth of primary tumors were not different from those seen in normal mice, but the rate of tumor progression was slowed and metastatic ability was almost completely abrogated when compared with mice that contained normal numbers of macrophages. Overexpression of CSF-1 in wild-type mice also accelerated tumor progression and increased rates of metastasis (17). Another study has shown that CSF-1 promotes tissue invasion by enhancing ECM-degrading pro-teinase MMP-2 production by lung cancer cells (38). In some instances, malignant cells coexpress CSF-1 and CSF-1R, raising the possibility of autocrine growth control by CSF-1 in the development of these malignancies (39).
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