Modulation of tumor angiogenesis by stem cell factor

Mast cells accumulate within solid tumors and can release many angiogenic f actors, suggesting that they may modulate vascularization of tumors. Stem c ell factor (SCF) stimulates mast cell migration, proliferation, and degranu lation and therefore may influence mast cell behavior within tumors. We inv estigated the contribution of SCF to tumor angiogenesis by manipulating its level in mammary tumors. Sense or antisense cDNA fragments of rat SCF were ligated into an episomal expression vector. Ethylnitrosourea-induced rat m ammary tumor cell lines were transfected with vector containing either cont rol (no insert, C-P), sense (S-P), or antisense (AS-P) SCF DNA. The functio nal nature of the transfectants was confirmed by measuring SCP in cell lysa tes and conditioned media. Immunohistochemical analysis of the tumors induc ed in Berlin-Druckrey rats by these transfected cells demonstrated that mas t cell number and microvascular density were significantly higher in S-P tu mors and significantly lower in AS-P tumors, compared with C-P tumors. The expression of von Willebrand factor, an endothelial cell marker, showed a s imilar pattern. AS-P tumors were significantly smaller than either C-P or S -P tumors. These data suggest that SCF modulates tumor growth and angiogene sis via the involvement of mast cells.