INTERLEUKIN-6 GENE-TRANSFECTED MOUSE MAMMARY ADENOCARCINOMA - TUMOR-CELL GROWTH AND METASTATIC POTENTIAL

Cells from the spontaneous metastatic TSA mammary adenocarcinoma of BA LB/C mouse were transfected with the murine (interleukin-6) IL6 gene. The clone (TSA-IL6) secreting the largest amount of IL6 displayed an i n vitro increased growth rate compared with that of TSA cells transfec ted with the neomycin resistance gene only (TSA-neo). TSA-IL6 cell col onies consisted mainly of fusiform cells and TSA-neo colonies of polyg onal cells. When subcutaneously (s.c.) injected in syngeneic mice, TSA -IL6 cells gave rise to tumours that grew significantly slower than TS A-neo cell tumours. Microscopically, TSA-IL6 tumours displayed a fasci cular pattern of growth, associated with a very scanty macrophage infi ltrate. S.c. TSA-IL6 rumours were significantly less metastatic than T SA-neo tumours. By contrast, following intravenous (i.v.) challenge, T SA-IL6 cells produced 5-7 times more lung metastases than TSA-neo cell s. The i.v. TSA-IL6 cell lung metastases showed a marked macrophage in filtrate and a rich vascularization. The high in vitro TSA-IL6 cell gr owth rate is attributable to the IL6-induced production of growth fact ors, some of which possess heparin-binding properties, such as amphire gulin. The differences in vascularization and macrophage infiltrate ma y underlie the observed differences between s.c. TSA-IL6 tumour growth with low spontaneous metastatic potential and the widespread growth o f i.v. metastasis. (C) 1997 by John Wiley & Sons, Ltd.