ECTOPIC PRODUCTION OF HEPARIN-BINDING GROWTH-FACTORS AND RECEPTORS FOR BASIC FIBROBLAST GROWTH-FACTOR BY RAT MAMMARY EPITHELIAL-CELL LINES DERIVED FROM MALIGNANT METASTATIC TUMORS

A rat mammary (Rama) epithelial cell line, Rama 704, derived from norm al rat mammary gland does not possess any detectable cell-surface rece ptors for basic fibroblast growth factor (bFGF), produces a barely det ectable level of bFGF mRNA and does not contain detectable levels of b FGF-like activity. Similar results have been obtained with the Rama 37 epithelial cells derived from benign tumours. However, 4 independentl y isolated epithelial cell lines derived from malignant rat mammary tu mours and their metastases possess receptors for bFGF and contain betw een 2 ng and 9 ng heparin-binding, growth-stimulatory activity per 10( 6) cells. The weakly metastatic Rama 600 cells possess high- and low-a ffinity receptors for bFGF, (K(D) 20 pM and 8 nM, respectively), while the moderately metastatic Rama 800 cells possess only high-affinity r eceptors (K(D) 40 pM). The moderately metastatic C18PLN and 267LU cell s, derived from metastases arising from benign Rama 37 cells which had been transfected with DNA from the malignant Rama 800 cells, also pos sess only high-affinity receptors (K(D) 36 pM and 80 pM, respectively) . Our results show that within the Rama system there is a correlation between the appearance of heparin-binding growth factors and of high-a ffinity but not low-affinity receptors for bFGF with the malignant phe notype. (C) 1993 Wiley-Liss, Inc.