Purification from a human hepatoma cell line of a basic fibroblast growth factor-like molecule that stimulates capillary endothelial cell plasminogen activator production, DNA synthesis, and migration.

Abstract

A 17,500-dalton protein which stimulates plasminogen activator production in cultured bovine capillary endothelial cells has been purified from a SK-Hep-l human hepatoma cell lysate by using heparin affinity chromatography and fast protein-liquid ion exchange chromatography. The purified molecule stimulated plasminogen activator production in a dose-dependent manner between 0.01 and 1 ng/ml. It also stimulated collagenase synthesis, DNA synthesis, and motility in capillary endothelial cells in the same concentration range. This molecule was identified as a basic fibroblast growth factor-like molecule on the basis of its biological activity, its affinity for heparin-Sepharose, and its cross-reactivity with a polyclonal antibody raised against the human placental basic fibroblast growth factor.

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…Various tumor cell lines express FGF2 [174,175] and the appearance of an angiogenic phenotype correlates with the export of FGF2 during the development of fibrosarcoma in a transgenic mouse model [176]. Antisense cDNAs for FGF2 and FGFR1 inhibit neovascularization and growth of human melanomas in nude mice [177].…”

“…Since then, 22 structurally-related members of the FGF family have been identified [8]. FGFs are pleiotropic factors acting on different cell types, including www.elsevier.com/locate/cytogfr Cytokine & Growth Factor Reviews 16 (2005) [159][160][161][162][163][164][165][166][167][168][169][170][171][172][173][174][175][176][177][178] endothelial cells, following interaction with heparan-sulfate proteoglycans (HSPGs) and tyrosine kinase FGF receptors (FGFRs). To date, more than 1200 PubMed-referenced papers related to FGFs and FGFRs in endothelial cells and during neovascularization have been published.…”

Differential expression of angiogenic cytokines by cell lines and primary cultures of human prostate cancer

“…17 bFGF expression in endothelial cells is up-regulated by human hepatoma or mouse sarcoma conditioned medium, and bFGF in turn increases u-PA production and cell motility. 18 TNF-a is pro-apoptotic to prostate epithelium, but it is also a strong inducer of proteolytic cytokine expression by human endothelial cells and is angioenic in vivo. 19,20 While the balance between these two different functions has not been elucidated, its expression by established cell lines and primary CaP cultures has not been compared.…”

Immunohistochemical localisation of tissue plasminogen activator in human brain tumours

“…The finding that t-PA was present in brain vessels adjacent to tumour indicates that its production is an intrinsic property of endothelium which is enhanced when it is stimulated to proliferate by tumour angiogenesis factors. A purified fibroblast growth factor-like substance derived from a human hepatoma cell line has recently been shown to promote angiogenesis in vivo and induce PA activity, enhance DNA synthesis and promote motility in confluent bovine endothelial cells (Presta et al, 1986). Lymphokines have also been shown to have a similar inductive effect on endothelium (Tiku & Tomasi, 1985).…”