IMPAIRED TUMOR-GROWTH IN COLONY-STIMULATING-FACTOR-1 (CSF-1)-DEFICIENT, MACROPHAGE-DEFICIENT OP OP MOUSE - EVIDENCE FOR A ROLE OF CSF-1-DEPENDENT MACROPHAGES IN FORMATION OF TUMOR STROMA/

Macrophages have been suggested to play a major role in the immune res ponse to cancer. They have also been suggested to stimulate the format ion of tumor stroma and to promote tumor vascularization. The availabi lity of the op/op mouse, which has no endogenous colony-stimulating fa ctor 1 (CSF-1) and which possesses a profound macrophage deficiency, p rovides a new model to verify these notions. Subcutaneous growth of tr ansplantable Lewis lung cancer (LLC) is markedly impaired in the op/op mice compared with normal littermates. Treatment of tumor-bearing op/ op mice with human recombinant CSF-1 corrects this impairment. Histolo gical analysis of tumors grown in op/op and normal mice revealed marke d differences. Tumors grown in op/op mice display a decreased mitotic index and pronounced necrosis, particularly hemorrhagic. Moreover, par ticularly in the op/op tumors, peculiar sinusoid-like abortive vessels (not filled with blood) have been observed. These tumors, in contrast to tumors grown in normal mice, are almost deprived of regular arteri es and veins. In contrast to tumors grown in normal mice, they exhibit almost no Sirius red-stained collagenous fibers and Gomori silver-sta ined reticular fibers. Our data suggest that the CSF-1-dependent macro phage subpopulation missing in op/op mice plays a primary role in supp orting tumor stroma formation and tumor vascularization in murine LLC tumors. (C) 1996 Wiley-Liss, Inc.