Tumor growth and angiogenesis induced by a secreted binding protein for fibroblast growth factors.
Basic fibroblast growth factor (bFGF) is a strong inducer of angiogenesis and thus may play an important role in the growth of solid tumors. However, bFGF is usually found immobilized on the extracellular matrix, and it is only partly understood how it is solubilized to reach and activate its extracellular receptors. We studied the potential contribution to this process by a secreted binding protein (BP) with high affinity for FGFs. An expression vector for BP was transfected into a human cell line (SW-13) that contains constitutively high levels of bFGF. The BP-expressing cells began to grow colonies in soft agar due to their autocrine stimulation by bFGF and released biologically active bFGF into their media. Furthermore, they grew into well vascularized tumors in athymic nude mice. In addition, we found the BP mRNA expressed at high levels in squamous cell carcinoma (SCC) tissues from patients and in SCC cell lines of different origin as well as in immortalized keratinocytes. However, we failed to detect BP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted BP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.
Czubayko
F
F
Vincent T. Lombardi Cancer Center, Department of Pharmacology, Georgetown University, Washington, D.C. 20007.
Smith
R V
RV
Chung
H C
HC
Wellstein
A
A
D016475:3T3 Cells; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D015152:Blotting, Northern; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D002352:Carrier Proteins / Q000096:biosynthesis / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism* / Q000494:pharmacology*; D015870:Gene Expression; D005822:Genetic Vectors; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000473:pathology; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D015183:Restriction Mapping; D014162:Transfection; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured
D002352:Carrier Proteins; D012333:RNA, Messenger; D016222:Fibroblast Growth Factor 2