Basic fibroblast growth factor modulates the expression of glycophorin A and c-kit and inhibits erythroid differentiation in K562 cells

Basic fibroblast growth factor (bFGF) is produced by bone marrow stromal ce lls as well as by normal and leukemic hematopoietic cells. In this study, w e examine the direct effects of bFGF on erythroid differentiation in K562 c ells in order to determine whether bFGF can promote the expression of a pri mitive phenotype. Low levels of bFGF inhibited erythroid differentiation as evidenced by decreased expression of glycophorin A and increased expressio n of c-kit. bFGF also increased both the numbers and the sizes of colonies of K562 cells in soft agar assays. The addition of TGF-beta to these cells induced erythroid differentiation which resulted in an increase in glycopho rin A and a decrease in c-kit. The simultaneous addition of bFGF and TGF-be ta to K562 cells prevented both the TGF-beta -mediated increase in glycopho rin A expression and the decrease in c-kit expression associated with eryth roid differentiation. bFGF antagonised the TGF-beta -mediated promotion of erythroid differentiation in K562 cells in a dose dependent manner and thes e two cytokines counteracted each other on an approximately molar basis. Th ese results indicate that bFGF alone increases expression of c-kit and prom otes a primitive phenotype in K562 cells. In addition, bFGF counteracts the effects of differentiation-inducing cytokines, such as TGF-beta, on hemato poietic cells. It is therefore possible that enhanced production of bFGF by leukemic cells could contribute to their neoplastic phenotype by opposing the effects of negative regulators or cytokines that induce differentiation . (C) 2002 Wiley-Liss, Inc.