INVASION OF HUMAN COLORECTAL-CARCINOMA CELLS IS PROMOTED BY ENDOGENOUS BASIC FIBROBLAST GROWTH-FACTOR

The growth-stimulatory and invasion-promoting effects of basic fibrobl ast growth factor (bFGF) were examined in 2 series of related human co lon carcinoma cell lines (HCT116A, HCT116B and 20-10-1 as well as and LS180, LS174T and ARK1A) that exhibit different invasive potentials. T he invasive cell lines 20-10-1 and ARK1A grew more rapidly than their non-invasive counterparts; exogenously added bFGF stimulated the proli feration of all the cells. When extracts of the cells were fractionate d on columns of heparin-Sepharose, bFGF-like activity was found in ext racts from each cell line. The amount of bFGF-like growth-stimulatory activity was greater in the more invasive cells: the invasive cells 20 -10-1 contained 35-fold more activity than the non-invasive HCT116A ce lls, and the ARK1A cells contained 15-fold more activity than LS180 ce lls. Relatively small amounts of 6FGF-like activity were recovered fro m medium conditioned by the invasive cells. The bFGF-like growth-stimu latory activity from the cell extracts was neutralised by an antibody to bFGF, and immunoblotting revealed the presence of an 18 kDa immunor eactive polypeptide, consistent with the presence of bFGF in the cell extracts. Exogenously added bFGF caused the usually non-invasive HCT11 6A cells to invade collagen gels. The HCT116B and 20-10-1 cells that w ere naturally invasive in a collagen gel assay also showed increased l evels of invasiveness in the presence of bFGF, but an antibody that ne utralised the activity of bFGF reduced the constitutive invasiveness o f these cells. Our results suggest a causal relationship between the e ndogenous production of bFGF and the invasive potential of human colon carcinoma cells. (C) 1997 Wiley-Liss, Inc.