Expression and function of prolactin and its receptor in glioblastoma cells

ALEJANDRO NICOLA; ANTONELA ASAD; VINCENT GOFFIN; JIMENA FERRARIS; SANTIAGO JORDI ORRILLO; DANIEL PISERA; CAMILA ZUCCATO; ADRIANA SEILICOVICH; MARIANELA CANDOLFI

Ciudad de Buenos Aires

Congreso; Reunión conjunta de Sociedades de Biociencia; 2017

Sociedad Argentina de Investigación Clínica

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 pathogeny of GBM is not well understood. 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 found that GBM cells can secrete prolactin and that the prolactin receptor (RPRL) antagonist ∆1?9-G129R-hPRL reduces their proliferation rate. Now we aimed to assess the expression of RPRL in GBM cells and the effect of PRL on the sensitivity of GBM 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 determine the characteristics of their signaling. We assessed the expression of these isoforms by Western Blot and detected abundant expression of short RPRL isoform in 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 (5µM) and temozolomide (15µM) in human U251 GBM cells (p