Expression and function of prolactin and its receptor in glioblastoma cells.

ASAD, ANTONELA S.; NICOLA CANDIA, ALEJANDRO J.; ZUCCATO, CAMILA; ORRILLO, SJ.; GOFFIN, V.; SEILICOVICH, ADRIANA; PISERA, DA.; FERRARIS, J.; CANDOLFI, M

Congreso; Reunión conjunta de sociedades de biociencias; LXII Reunión Anual de la Sociedad Argentina de Investigación Clínica (SAIC).; 2017

Glioblastoma multiforme (GBM) is the most common and aggressive primary brain cancer in adults. In spite of improved standard of care (surgery, chemotherapy and radiation) the median survival of GBM patients remains dismal. Prolactin (PRL) has been recently associated to the development of several hormone-dependent cancers. However, its role in the pathogenesis of GBM remains unknown. The expression of PRL has been detected in human GBM biopsies and over 30% of brain cancer patients exhibit hyperprolactinemia, which has positive correlation with the proliferation index and the vascular density of brain tumors. We have previously observed that GBM cells secrete PRL and that the PRL receptor (RPRL) antagonist ∆1?9-G129R-hPRL reduces their proliferation rate. Now we aimed to assess the expression of RPRL in human GBM cells and the effect of PRL on the sensitivity of these cells to chemotherapeutic agents. Expression of RPRL was detected by immunofluorescence in human U251 GBM cells. Various isoforms of RPRL have been reported, which are produced by alternative splicing and differ in the length of their intracellular domain, which in turn determines the characteristics of their signaling. We assessed the expression of these isoforms by Western blot and detected abundant expression of short RPRL isoform in U251 GBM cells. We next evaluated the effect of recombinant PRL and ∆1?9-G129R-hPRL on the sensitivity of human GBM cells to chemotherapeutic drugs. We found that addition of recombinant PRL (100-500 ng/ml) reduced the cytotoxic effect of Cisplatin (5 µM) and Temozolomide (15 µM) in U251 GBM cells (p<0.05), as assessed by MTT assay. On the other hand, ∆1?9-G129R-hPRL (5 µg/ml) reduced the viability and increased the cytotoxic effect of Cisplatin in human U251 and U87 GBM cells (p<0.05). Our findings suggest that locally synthesized PRL and its receptor could constitute a therapeutic target to improve the sensitivity of GBM cells to antineoplastic agents.