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

Abstract

Basic fibroblast growth factor (bFGF) is produced by bone marrow stromal cells as well as by normal and leukemic hematopoietic cells. In this study, we examine the direct effects of bFGF on erythroid differentiation in K562 cells in order to determine whether bFGF can promote the expression of a primitive phenotype. Low levels of bFGF inhibited erythroid differentiation as evidenced by decreased expression of glycophorin A and increased expression 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 glycophorin A and a decrease in c-kit. The simultaneous addition of bFGF and TGF-beta to K562 cells prevented both the TGF-beta-mediated increase in glycophorin A expression and the decrease in c-kit expression associated with erythroid differentiation. bFGF antagonised the TGF-beta-mediated promotion of erythroid differentiation in K562 cells in a dose dependent manner and these two cytokines counteracted each other on an approximately molar basis. These results indicate that bFGF alone increases expression of c-kit and promotes a primitive phenotype in K562 cells. In addition, bFGF counteracts the effects of differentiation-inducing cytokines, such as TGF-beta, on hematopoietic 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.

Deregulation of Flk-1/vascular endothelial growth factor receptor-2 in fibroblast growth factor receptor-1-deficient vascular stem cell development

“…tissues, and respond to FGF-2 (Cross and Claesson-Welsh, 2001;Burger et al, 2002). However, the role of FGF-2/FGFR-1 in vascular development remains controversial and it has not been clarified through genetic analyses.…”

TGF‐β and stem cell factor regulate cell proliferation in the proximal stem cell niche

“…The addition of TGF-β to a rat prostate basal cell line in the absence of mitogens induces differentiation while the presence of mitogens, such as IGF-1, suppresses TGF-β-induced differentiation, promoting a more primitive basal phenotype (40). Similarly Narine et al (41) demonstrated that either EGF or FGF-2 ablated TGF-β-induced growth inhibition of fibroblast proliferation and FGF-2 inhibited differentiation, as evidenced by loss of alpha smooth muscle actin expression, while Burger et al (42) demonstrated that FGF-2 maintains erythroid cells in a primitive state while TGF-β promotes their differentiation. SCF and its receptor, c-Kit, have been implicated as regulators of cellular proliferation and differentiation of progenitor cells in a variety of systems, including hematopoiesis, gametogenesis and melanogenesis (26,43,44).…”

IL-1β, TNF-α, TGF-β, and bFGF expression in bone biopsies before and after parathyroidectomy

“…Purif 13:135-146, 1995 6. Pfeilschifter J, Mundy GR, Roodman GD: Interleukin 1 and by bone marrow stromal cells [46]. After bone resorption tumor necrosis factor stimulate the formation of human osteoclastprocesses, latent factors, including bFGF, stimulate the like cells in vitro.…”