Instituto de Investigaciones Biomédicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina.
Max Planck Laboratory for Structural Biology, Chemistry and Molecular Biophysics of Rosario (MPLbioR), Universidad Nacional de Rosario, Rosario, Argentina.
Sci Rep. 2019 Dec 20;9(1):19578. doi: 10.1038/s41598-019-55860-x.
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 GBM pathogenesis. We detected PRL and PRLR in all GBM cell lines tested. PRLR activation or overexpression using plasmid transfection increased proliferation, viability, clonogenicity, chemoresistance and matrix metalloproteinase activity in GBM cells, while PRLR antagonist ∆1-9-G129R-hPRL reduced their proliferation, viability, chemoresistance and migration. Meta-analysis of transcriptomic data indicated that PRLR was expressed in all grade II-III glioma (GII-III) and GBM samples. PRL was upregulated in GBM biopsies when compared to GII-III. While in the general population tumour PRL/PRLR expression did not correlate with patient survival, biological sex-stratified analyses revealed that male patients with PRL/PRLR GBM performed worse than PRL/PRLR GBM. In contrast, all male PRL/PRLR GII-III patients were alive whereas only 30% of PRL/PRLR GII-III patients survived after 100 months. Our study suggests that PRLR may be involved in GBM pathogenesis and could constitute a therapeutic target for its treatment. Our findings also support the notion that sexual dimorphism should be taken into account to improve the care of GBM patients.
虽然催乳素（PRL）及其受体（PRLR）已在多形性胶质母细胞瘤（GBM）中被检测到，但它们在其发病机制中的作用仍不清楚。我们的目的是探讨它们在 GBM 发病机制中的作用。我们检测了所有测试的 GBM 细胞系中的 PRL 和 PRLR。使用质粒转染激活或过表达 PRLR 可增加 GBM 细胞的增殖、活力、克隆形成能力、化学抗性和基质金属蛋白酶活性，而 PRLR 拮抗剂 ∆1-9-G129R-hPRL 则降低了它们的增殖、活力、化学抗性和迁移能力。转录组数据分析的荟萃分析表明，PRLR 在所有 II-III 级胶质瘤（GII-III）和 GBM 样本中均有表达。与 GII-III 相比，GBM 活检中的 PRL 上调。虽然在普通人群中，肿瘤 PRL/PRLR 表达与患者生存无关，但按生物学性别分层分析显示，PRL/PRLR GBM 的男性患者比 PRL/PRLR GBM 的男性患者预后更差。相比之下，所有 PRL/PRLR GII-III 的男性患者都存活，而仅 30%的 PRL/PRLR GII-III 患者在 100 个月后存活。我们的研究表明，PRLR 可能参与 GBM 的发病机制，并可能成为其治疗的治疗靶点。我们的研究结果还支持这样一种观点，即应该考虑性别二态性来改善 GBM 患者的护理。
