PAPP-A proteolytic activity enhances IGF bioactivity in ascites from women with ovarian carcinoma

摘要: Pregnancy-associated plasma protein-A (PAPP-A) stimulates insulin-like growth factor (IGF) action through proteolysis of IGF-binding protein (IGFBP)-4. In experimental animals, PAPP-A accelerates ovarian tumor by this mechanism. To investigate the effect in humans, we compared serum and ascites from 22 women with carcinoma. We found that contained 46-fold higher levels as to (P < 0.001). The majority (80%) was enzymatically active. This is supported finding more cleaved than intact IGFBP-4 0.03). Ascites potent activating IGF-I receptor (IGF-IR) vitro (+31%, P 0.05); 8 patients two-fold. contrast, similar immunoreactive IGF-I, lower IGF-II Immunohistochemistry demonstrated presence IGF-IR all but one tumor, whereas tumors expressed PAPP-A, IGFBP-4, IGF-II. Addition recombinant increased cleavage enhanced activation 0.05). conclusion, human express IGFs these proteins are also present ascites. suggest both soluble tissue-associated serve increase IGF bioactivity and, thereby, stimulate IGF-IR-mediated growth.