Stimulation of prolactin receptor induces STAT-5 phosphorylation and cellular invasion in glioblastoma multiforme

// Amira Alkharusi 1, 2 , Shengze Yu 3 , Natalia Landazuri 4 , Fahad Zadjali 2 , Belghis Davodi 4 , Thomas Nystrom 1 , Torbjorn Graslund 3 , Afsar Rahbar 4 , Gunnar Norstedt 5 1 Department of Clinical Science and Education, Sodersjukhuset, Karolinska Institutet, Stockholm, Sweden 2 Sultan Qaboos University, College of Medicine and Health Sciences, Muscat, Oman 3 School of Biotechnology, KTH - Royal Institute of Technology, Stockholm, Sweden 4 Department of Medicine, Exp Cardiovascular Research Unit and Department of Neurology, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden 5 Department of Women’s and Children’s Health, Karolinska Institutet, Stockholm, Sweden Correspondence to: Gunnar Norstedt, email: gunnar.norstedt@ki.se Keywords: prolactin, prolactin receptor, prolactin receptor antagonist, STAT5, GBM Received: January 28, 2016 Accepted: October 10, 2016 Published: October 24, 2016 ABSTRACT Glioblastoma multiforme (GBM) is the most common and aggressive primary brain tumor in humans and is characterized with poor outcome. In this study, we investigated components of prolactin (Prl) system in cell models of GBM and in histological tissue sections obtained from GBM patients. Expression of Prolactin receptor (PrlR) was detected at high levels in U251-MG, at low levels in U87-MG and barely detectable in U373 cell lines and in 66% of brain tumor tissues from 32 GBM patients by immunohistochemical technique. In addition, stimulation of U251-MG and U87-MG cells but not U373 with Prl resulted in increased STAT5 phosphorylation and only in U251-MG cells with increased cellular invasion. Furthermore, STAT5 phosphorylation and cellular invasion induced in Prl stimulated cells were significantly reduced by using a Prl receptor antagonist that consists of Prl with four amino acid replacements. We conclude that Prl receptor is expressed at different levels in the majority of GBM tumors and that blocking of PrlR in U251-MG cells significantly reduce cellular invasion.