TUMOR-GROWTH AND ANGIOGENESIS INDUCED BY A SECRETED BINDING-PROTEIN FOR FIBROBLAST GROWTH-FACTORS

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.