Diverse effects of phospholipase A2 receptor expression on LNCaP and PC-3 prostate cancer cell growth in vitro and in vivo

Research output: Contribution to journalResearch articleContributedpeer-review

Contributors

  • Markus Friedemann - , Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden (Author)
  • Brit Nacke - , University Hospital Carl Gustav Carus Dresden (Author)
  • Albert Hagelgans - , University Hospital Carl Gustav Carus Dresden (Author)
  • Carsten Jandeck - , University Hospital Carl Gustav Carus Dresden (Author)
  • Nicole Bechmann - , Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden (Author)
  • Martin Ullrich - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Birgit Belter - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Christin Neuber - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Olga Sukocheva - , Flinders University (Author)
  • Jens Pietzsch - , Helmholtz-Zentrum Dresden-Rossendorf (Author)
  • Mario Menschikowski - , Institute of Clinical Chemistry and Laboratory Medicine, University Hospital Carl Gustav Carus Dresden (Author)

Abstract

Physiological and pathophysiological functions of the phospholipase A2 receptor 1 (PLA2R1) are still not completely understood. To elucidate PLA2R1's function in prostate carcinoma, the receptor was ectopically overexpressed in LNCaP with silenced PLA2R1, and diminished in PC-3 cells with constitutively increased PLA2R1 expression relative to normal prostate epithelial cells. LNCaP cells were transfected to overexpress PLA2R1 (LNCaP-PLA2R1) and compared to control vector transfected cells (LNCaP-Ctrl). Alternatively, a CRISPR/Cas9-knockdown of PLA2R1 was achieved in PC-3 cells (PC-3 KD) and compared to the corresponding control-transfected cells (PC-3 Ctrl). The impact of PLA2R1 expression on proliferative and metastatic parameters was analysed in vitro. A pilot in vivo study addressed the effects of PLA2R1 in mice xenografted with transfected LNCaP and PC-3 cells. Cell viability/proliferation and motility were significantly increased in LNCaP-PLA2R1 and PC-3 Ctrl compared to LNCaP-Ctrl and PC-3 KD cells, respectively. However, levels of apoptosis, clonogenicity and cell invasion were reduced in LNCaP-PLA2R1 and PC-3 Ctrl cells. Gene expression analysis revealed an up-regulation of fibronectin 1 (FN1), TWIST homolog 1 (TWIST1), and cyclin-dependent kinase 6 (CDK6) in LNCaP-PLA2R1. In LNCaP xenografts, PLA2R1-dependent regulation of clonogenicity appeared to outweigh the receptor's pro-oncogenic properties, resulting in decreased tumour growth, supporting the tumour-suppressive role of PLA2R1. Alternatively, PC-3 Ctrl xenografts exhibited faster tumour growth compared to PC-3 KD cells, suggesting a pro-oncogenic effect of endogenous PLA2R1 expression. The differential growth-regulatory effects of PLA2R1 may be mediated by FN1, TWIST1, and CDK6 expression, although further investigation is required.

Details

Original languageEnglish
Pages (from-to)35983-35996
Number of pages14
JournalOncotarget
Volume9
Issue number89
Publication statusPublished - 13 Nov 2018
Peer-reviewedYes

External IDs

PubMedCentral PMC6267604
Scopus 85056587889
ORCID /0000-0002-6932-333X/work/148144979

Keywords

Sustainable Development Goals