F. Czubayko et al., TUMOR-GROWTH AND ANGIOGENESIS INDUCED BY A SECRETED BINDING-PROTEIN FOR FIBROBLAST GROWTH-FACTORS, The Journal of biological chemistry, 269(45), 1994, pp. 28243-28248
Basic fibroblast growth factor (bFGF) is a strong inducer of angiogene
sis and thus may play an important role in the growth of solid tumors.
However, bFGF is usually found immobilized on the extracellular matri
x, and it is only partly understood how it is solubilized to reach and
activate its extracellular receptors. We studied the potential contri
bution to this process by a secreted binding protein (BP) with high af
finity for FGFs. An expression vector for BP was transfected into a hu
man cell line (SW-13) that contains constitutively high levels of bFGF
. The BP-expressing cells began to grow colonies in soft agar due to t
heir autocrine stimulation by bFGF and released biologically active bF
GF into their media. Furthermore, they grew into well vascularized tum
ors 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 k
eratinocytes. However, we failed to detect EP mRNA in normal adult tis
sues or in a number of non-SCC tumor cell lines. Expression of the sec
reted EP appears to be a mechanism through which immobilized FGF can b
e activated to support tumor growth and angiogenesis.