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TUMOR-GROWTH AND ANGIOGENESIS INDUCED BY A SECRETED BINDING-PROTEIN FOR FIBROBLAST GROWTH-FACTORS
Author(s): CZUBAYKO F, SMITH RV, CHUNG HC, WELLSTEIN A
Source: JOURNAL OF BIOLOGICAL CHEMISTRY    Volume: 269    Issue: 45    Pages: 28243-28248    Published: NOV 11 1994  
Times Cited: 89     References: 32     
Abstract: 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 EP mRNA in normal adult tissues or in a number of non-SCC tumor cell lines. Expression of the secreted EP appears to be a mechanism through which immobilized FGF can be activated to support tumor growth and angiogenesis.
Document Type: Article
Language: English
Addresses:
1. GEORGETOWN UNIV, VT LOMBARDI CANC CTR, DEPT PHARMACOL, WASHINGTON, DC 20007 USA
2. GEORGETOWN UNIV, DEPT OTOLARYNGOL HEAD & NECK SURG, WASHINGTON, DC 20007 USA
Publisher: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC, 9650 ROCKVILLE PIKE, BETHESDA, MD 20814
Subject Category: Biochemistry & Molecular Biology
IDS Number: PV772
ISSN: 0021-9258
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