IDENTIFICATION OF EGF AS AN ANGIOGENIC FACTOR PRESENT IN CONDITIONED MEDIUM FROM HUMAN SALIVARY-GLAND ADENOCARCINOMA CELL CLONES WITH VARYING DEGREES OF METASTATIC POTENTIAL

We have previously shown that conditioned medium (CM) from metastasizi ng human salivary gland adenocarcinoma cell clones contains factor(s) that stimulate the proliferation and migration of bovine aortic endoth elial (BAE) cells, and inhibit the production of collagenases by BAE c ells (Azuma M. et al. (1993) Cancer Lett., 73, 85-93). To further char acterize this, we evaluated the expression level of epidermal growth f actor (EGF) secreted by a non-metastasizing cell clone (HSGc) and its metastasizing cell clones, and analysed the effect of EGF on the biolo gic behaviors of BAE cells. When the secretion of EGF by cell clones w as estimated by enzyme-linked immunosorbent assay, metastasizing cell clones released a large amount of EGF as compared with HSGc. However, the number of EGF receptor was detected consistently at a level that w as similar in all cell clones. With regard to the effect of EGF on the malignant potential of cell clones such as proteolytic aggressiveness , EGF did not affect the secretion of both collagenases and their inhi bitor from cell clones. Alternatively, exogenous EGF stimulated the pr oliferation and migration of BAE cells, and inhibited the secretion of collagenases from BAE cells. Neutralization with a neutralizing antib ody of EGF released into CM abolished the inhibitory effect of CM on t he secretion of collagenases from BAE cells. Thus, the CM-contained fa ctor, which is responsible for the induction of biologic behaviors of BAE cells, can be attributed to EGF.