Trophic role of prolactin in glioblastoma cells

A.ASAD; S.ORRILLO; A.J.NICOLA CANDIA; D. PISERA; V. GOFFIN; J. FERRARIS; C.ZUCATTO; A. SEILICOVICH; M. CANDOLFI

Simposio; The role of glial cells in health and disease of the Nervous System: Clinical and Basic Science walking together; 2017

Glioblastoma multiforme (GBM) is a glial brain cancer that constitutes the most frequent primary brain tumor in adults. Despite improvements in the current standard of care, the median survival of GBM patients remains dismal. Recently, prolactin (PRL) and its receptor (RPRL) have been detected in GBM human biopsies. Although PRL has been associated to the development of several hormone-dependent cancers, its role in the pathogenesis of GBM is poorly understood. Over 30% of brain cancer patients exhibit hyperprolactinemia, which has positive correlation with the proliferation index and the vascular density of brain tumors. In this project we aimed to evaluate the expression of PRL and RPRL in GBM cells and their role in the survival and chemoresistance of these cells. We observed that human, rat and mouse GBM cells lines express and secrete PRL (immunofluorescence, RIA). RPRL was detected by immunofluorescence in human GBM cells. We assessed the expression of RPRL isoforms by Western blot and detected abundant expression of short RPRL isoform in mouse and human GBM cells. To evaluate the autocrine/paracrine effect of GBM-secreted PRL, we used the RPRL antagonist ∆1?9-G129R-hPRL. Blockade of PRL action reduced the proliferation rate of GBM cells. We next evaluated the effect of recombinant PRL and ∆1?9-G129R-hPRL on the chemosensitivity of GBM cells. Addition of recombinant PRL reduced the cytotoxic effect of Cisplatin and Temozolomide, while ∆1?9-G129R-hPRL increased the apoptotic effect of Cisplatin in human GBM cells (MTT). Our findings suggest that locally synthesized PRL and its receptor could constitute therapeutic targets to improve the sensitivity of GBM cells to antineoplastic agents.