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

Oncotarget
Jacob ThomsenJ Frystyk

Abstract

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 growth by this mechanism. To investigate the effect of PAPP-A in humans, we compared serum and ascites from 22 women with ovarian carcinoma. We found that ascites contained 46-fold higher PAPP-A levels as compared to serum (P < 0.001). The majority (80%) of PAPP-A was enzymatically active. This is supported by the finding that ascites contained more cleaved than intact IGFBP-4 (P < 0.03). Ascites was more potent than serum in activating the IGF-I receptor (IGF-IR) in vitro (+31%, P < 0.05); in 8 of 22 patients by more than two-fold. In contrast, ascites contained similar levels of immunoreactive IGF-I, and lower levels of IGF-II (P < 0.001). Immunohistochemistry demonstrated the presence of IGF-IR in all but one tumor, whereas all tumors expressed PAPP-A, IGFBP-4, IGF-I and IGF-II. Addition of recombinant PAPP-A to ascites increased the cleavage of IGFBP-4 and enhanced IGF-IR activation (P < 0.05). In conclusion, human ovarian tumors express PAPP-A, IGFBP-4 and IGFs and these proteins are also present in ascites. We sugge...Continue Reading

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Citations

Sep 29, 2020·Frontiers in Endocrinology·Rikke HjortebjergJan Frystyk
Dec 31, 2016·Aging Cell·Cheryl A Conover, Claus Oxvig
Sep 26, 2017·The Journal of Clinical Endocrinology and Metabolism·Nilani RamshankerJan Frystyk
Sep 3, 2020·The Journal of Clinical Endocrinology and Metabolism·Rikke HjortebjergJo G R De Mey
Aug 15, 2020·Scientific Reports·Prashanth PrithvirajAparna Jayachandran
May 31, 2018·Journal of Molecular Endocrinology·Cheryl A Conover, Claus Oxvig
Sep 8, 2019·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Joseph A M J L JanssenMichael P Brugts
Jul 22, 2020·Growth Hormone & IGF Research : Official Journal of the Growth Hormone Research Society and the International IGF Research Society·Jan FrystykRikke Hjortebjerg

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