TISSUE DISTRIBUTION OF HUMAN GLIOSTATIN PLATELET-DERIVED ENDOTHELIAL-CELL GROWTH-FACTOR (PD-ECGF) AND ITS DRUG-INDUCED EXPRESSION/

Human tissue contents of gliostatin/platelet-derived endothelial cell growth factor (PD-ECGF) and its drug-induced expression in tumor cells were currently examined by a sandwich enzyme immunoassay (EIA) system and a reverse transcription-polymerase chain reaction (RT-PCR) method . Gliostatin/PD-ECGF was found to distribute in rather ubiquitous than specific human tissues and organs, with a relatively high levels in t he tissues of digestive system (esophagus and rectum), brain, spleen, bladder and lung, but not in gall bladder, aorta, muscle, fat and kidn ey. Most of examined human tumor cell lines showed 4- or 5-fold higher contents (21.5 +/- 3.9 ng/mg protein) than normal tissue contents (4. 4 +/- 1.1 ng/mg protein) on the average. While gliostatin/PD-ECGF is k nown to lack a signal sequence, some tumor cells (A431 and MKN74) appe ared to release it into the conditioned medium. Expression of gliostat in/PD-ECGF in epidermoid carcinoma cell (A431) and stomach cancer cell (MKN45) was induced by dibutyryl cyclic AMP and phorbol ester, and un iquely in MKN45 by hydrocortisone. In particular, this hydrocortisone specifically caused an increase of the apparent secretion of MKN74 wit hout its cytotoxic effects, suggesting a possible secretion of gliosta tin/PD-ECGF in the restricted but not universal cell line. Biological significance on the chemical induction of gliostatin/PD-ECGF in tumor cells and on its extracellular secretion are discussed.