Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: Autocrine effects on cell proliferation and migration
Article first published online: 12 JAN 2011
Copyright © 2011 Wiley-Liss, Inc.
Volume 71, Issue 10, pages 1084–1096, July 2011
How to Cite
Vo, B. T. and Khan, S. A. (2011), Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: Autocrine effects on cell proliferation and migration. Prostate, 71: 1084–1096. doi: 10.1002/pros.21326
- Issue published online: 9 MAY 2011
- Article first published online: 12 JAN 2011
- Manuscript Accepted: 22 NOV 2010
- Manuscript Received: 15 JUL 2010
- NIH/NCRR/RCMI. Grant Number: #2G12RR003062
- NIH P20. Grant Number: #5P20MD002285-02
- DOD. Grant Number: #W8I-08-1-0077
- NIGMS/NIH. Grant Number: #5R25GM0604
- prostate cancer;
- cancer stem cells;
- cell proliferation;
- cell migration
Nodal, a TGFβ like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. Nodal has been implicated in cancer progression; however, there is no information on expression and functions of Nodal in prostate cancer. In this study, we have investigated the expression of Nodal, its receptors, and its effects on proliferation and migration of human prostate cells.
RT-PCR, qPCR, and Western blot analyses were performed to analyze expression of Nodal and Nodal receptors and its effects on phosphorylation of Smad2/3 in prostate cells. The effects on proliferation and migration were determined by 3H-Thymidine incorporation and cell migration assays in the presence or absence of Nodal receptor inhibitor (SB431542).
Nodal was highly expressed in WPE, DU145, LNCaP, and LNCaP-C81 cells with low expression in RWPE1 and RWPE2 cells, but not in PREC, PC3 and PC3M cells. Nodal receptors are expressed at varying levels in all prostate cells. Treatment with exogenous Nodal induced phosphorylation of Smad2/3 in WPE, DU145, and PC3 cells, which was blocked by SB431542. Nodal dose-dependently inhibited proliferation of WPE, RWPE1 and DU145 cells, but not LNCaP and PC3 cells. Nodal induced cell migration in PC3 cells, which was inhibited by SB431542; Nodal had no effect on cell migration in WPE and DU145 cells. The effects of Nodal on cell proliferation and migration are mediated via ALK4 and ActRII/ActRIIB receptors and Smad 2/3 phosphorylation.
Nodal may function as an autocrine regulator of proliferation and migration of prostate cancer cells. Prostate 71:1084–1096, 2011. © 2011 Wiley-Liss, Inc.