Coordinated modulation of the fibroblast growth factor dual receptor mechanism during transformation from human colon adenoma to carcinoma

Basic fibroblast growth factor (bFGF) is dependent on heparan sulphate for its ability to activate the cell surface signal transducing receptor. We ha ve investigated the FGF dual receptor mechanism in a novel model of the tra nsformation from human colon adenoma to carcinoma In vitro. Reverse transcr iption-polymerase chain reaction showed that mRNA for FGF receptors 1 and 2 were expressed in both the adenoma and carcinoma cells whereas immunocytoc hemistry showed that the expression of the FGF R1 was reduced significantly in the carcinoma cells. We have reported previously that the composition a nd sequence of human colon adenoma and carcinoma heparan sulphate (HS) diff er in a defined and specific manner. The functional significance of these c hanges was assessed by affinity co-electrophoresis, which showed that the a ffinity of adenoma HS for bFGF was 10-fold greater than that of the carcino ma HS (K-d 220 nM vs. 2493 nM, respectively). In addition, Northern studies of the expression of syndecan 1 and 4 mRNA showed that proteoglycan core p rotein expression was reduced significantly in the carcinoma cells. These f indings were associated with a reduced biological response to bFGF in the c arcinoma cells that could be partially reversed by the addition of exogenou s heparin, suggesting that both the proteoglycan and signal transducing rec eptor control the cells' response to bFGF. (C) 1999 Wiley-Liss, Inc.