Mitogenicity of human fibroblasts in vivo for human breast cancer cells

Stromal factors have been implicated in the regulation of mammary epithelial cell behaviour, but their influence on human breast cancer is unknown. Fibroblasts were grown in monolayer cell culture from explants of benign and malignant breast tissue and normal skin. MCF7 human breast cancer cells alone (2 X 10(6) cells) or in combination with live fibroblasts (MCF7 + F) were inoculated into the mammary fat pads of 6-8-week-old female nude mice. After 5 weeks tumours were excised, weighed and fixed for histological examination. Addition of live breast fibroblasts significantly increased the retrieval (127/135 versus 52/106, P less than 0.01, chi 2 test) and growth (tumour weight 174 +/- 11 versus 41 +/- 4 mg, mean +/- s.e.m., P less than 0.01, Mann-Whitney U test) of subsequent tumours. Histological examination did not reveal any morphological difference between the two tumour groups. Injection of fibroblasts alone did not produce tumours. Addition of skin fibroblasts was also stimulatory. Glutaraldehyde-killed fibroblasts increased tumour take but did not stimulate tumour growth. Mononuclear blood leucocytes were ineffective. The results demonstrate that, in this model, fibroblasts exert stimulatory influences on human breast cancer xenograft growth and development.