Prolactin and its receptor as therapeutic targets in glioblastoma multiforme

ASAD, ANTONELA SOFÍA; NICOLA CANDIA, ALEJANDRO JAVIER; GONZALEZ, NAZARENO; ZUCCATO, CAMILA FLORENCIA; ABT, ARACELI; ORRILLO, SANTIAGO JORDI; LASTRA, YAEL; DE SIMONE, EMILIO; BOUTILLON, FLORENCE; GOFFIN, VINCENT; SEILICOVICH, ADRIANA; PISERA, DANIEL ALBERTO; FERRARIS, MARÍA JIMENA; CANDOLFI, MARIANELA

Scientific Reports

Nature research

Lugar: Londres; Año: 2019 vol. 9 p. 1 - 16

Although prolactin (PRL) and its receptor (PRLR) have been detected in glioblastoma multiforme(GBM), their role in its pathogenesis remains unclear. Our aim was to explore their contribution in GBMpathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpressionusing plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrixmetalloproteinase activity in GBM cells, while PRLR antagonist Δ1?9-G129R-hPRL reduced theirproliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicatedthat PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated inGBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expressiondid not correlate with patient survival, biological sex-stratified analyses revealed that male patientswith PRL+/PRLRHIGH GBM performed worse than PRL+/PRLRLOW GBM. In contrast, all male PRL+/PRLRHIGH GII-III patients were alive whereas only 30% of PRL+/PRLRLOW GII-III patients survived after100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitutea therapeutic target for its treatment. Our findings also support the notion that sexual dimorphismshould be taken into account to improve the care of GBM patients.