HEPARIN RECEPTORS IN 2 MURINE MAMMARY ADENOCARCINOMAS WITH DIFFERENT METASTATIC ABILITY - RELATIONSHIP WITH GROWTH-INHIBITION

Binding of heparin to primary cultured cells of two murine mammary ade nocarcinomas with low (M3) and high (MM3) lung, metastatic capacity wa s determined. Heparin binding was rapid, specific and saturable. MM3 c ells grown for 24 h in fetal calf serum (FCS)-free medium exhibited a higher number of binding sites for H-3-heparin [(11 +/- 1) x 10(5) sit es per cell] than M3 cells [(6.9 +/- 0.6) x 10(5) sites per cell], How ever, when M3 cells were grown in the presence of 2% FCS, they showed less heparin binding sites [(3.5 +/- 0.4) x 10(5) sites per cell]. In contrast, dissociation constants were very similar for MM3 and M3 cell s grown with or without FCS (K-d = 2-4 x 10(-9) M). Furthermore, hepar in inhibited MM3 and M3 cell growth both in the absence or presence of FCS. Competition studies showed that chemically modified heparins lac king antiproliferative effect (O-desulfated; O/N-desulfated N-acetylat ed and N-desulfated heparins) were not able to inhibit H-3-heparin bin ding. N-desulfated N-acetylated heparin, which had partial antiprolife rative effect, partially inhibited H-3-heparin binding, while heparin with a high antiproliferative activity inhibited more than 90% H-3-hep arin binding. The antiproliferative effect of heparin and chemically m odified heparins seems to be related to their binding ability to the c ell membrane.