ESA-SRB-AOTA 2019

Activin C inhibits ovarian and prostate cancer cell growth and expression is decreased in higher grade tumours (#192)

Karen L Reader 1 , David G Mottershead 2 , Helen D Nicholson 1
  1. Department of Pathology, University of Otago, Dunedin, Otago, Aotearoa New Zealand
  2. School of Pharmacy, Keele University, Newcastle-under-Lyme, Staffordshire, United Kingdom

Activins regulate the growth and differentiation of many tissues and expression has been shown to be dysregulated in some cancers. Reports of the effects of activin A on ovarian and prostate cancer cell growth are contradictory and little is known about the response of ovarian and prostate epithelial cells to activins B and C. We examined the effect of purified, full-length recombinant activin C on the growth and migration of ovarian and prostate cancer cell lines. The levels of activin A, B and C protein expression were compared between human epithelial ovarian cancer tumors of different International Federation of Gynecology and Obstetrics (FIGO) stages and between prostate adenocarcinomas with different Gleason scores using a digital immuno-reactive scoring method. The effect of activin A, activin C and their combination on gene expression in Ovcar3 cells was assessed using the NanoString nCounter Pan Cancer Pathway panel. Activin C treatment decreased cell number in three ovarian cancer cell lines and three prostate cell lines, but increased cell number in LNCaP cells. It had no effect on the migration of ovarian cancer cells. All three activins exhibited decreasing immuno-reactive scores with increasing FIGO stage in ovarian tumours. The immuno-reactive scores for activin B were generally higher in higher grade prostate tumours while activin C expression appeared to decrease with increasing Gleason pattern. Differential gene expression analysis showed that activin A and activin C have opposing effects on molecular pathways involved in cancer progression, including the DNA repair, chromatin modification, TGFB and hedgehog pathways. Activin C increased expression of BNIP3 mRNA and increased activated caspase 3/7 in Ovcar3 cells, suggesting this protein can inhibit cancer cell growth by increasing apoptosis. These findings highlight a potential prognostic and therapeutic role for activin C in ovarian and prostate cancer.