CONTRIBUTION OF HOST-DERIVED GROWTH-FACTORS TO IN-VIVO GROWTH OF A TRANSPLANTABLE MURINE MAMMARY-CARCINOMA

The contribution of host-derived growth factors to tumour growth in vi vo was studied using the transplantable murine mammary carcinoma, MT1, grown in syngeneic mice. Promotion of growth of the mammary carcinoma by a factor(s) from the host was evident in experiments in which the carcinoma cells were inoculated intraperitoneally. In this environment , tumours develop as multiple solid nodules, each probably arising fro m an individual cell or a small cluster of cells. Tumour growth was fo und to occur in the peritoneal cavity following inoculation of 10(3) c ells, but an inoculum of as few as ten cells grew if a leucocyte-rich exudate had first been induced. To determine which host-derived growth factors might contribute to growth of MTI, extracts of the tumour wer e first examined for growth factor activity. Fractionation of tumour e xtracts by either ion-exchange chromatography or gel filtration reveal ed several peaks of mitogenic activity, but none of this could be attr ibuted to epidermal growth factor (EGF). Accordingly, an anti-EGF anti body was tested as a putative inhibitor of tumour growth as any effect of this antibody could be ascribed to removal of EGF derived from the host. The antibody was found to have potent anti-tumour activity when tested against MT1 tumours that had been inoculated into the peritone al cavity. In contrast, the antibody had little effect on growth of th e discrete tumour mass which formed when MTI was transplanted subcutan eously. The results suggest that host-derived EGF contributes to estab lishment of microcolonies of MT1 carcinoma within the peritoneal cavit y. This may be directly, by providing growth factors to supplement tho se produced by the tumour until it reaches a certain critical mass to sustain autocrine growth, or indirectly, by affecting the production o f other growth-stimulatory factors or cytokines.