Table of Contents Author Guidelines Submit a Manuscript
Prostate Cancer
Volume 2011, Article ID 893208, 14 pages
http://dx.doi.org/10.1155/2011/893208
Research Article

Role of Heparan Sulfate 2-O-Sulfotransferase in Prostate Cancer Cell Proliferation, Invasion, and Growth Factor Signaling

Department of Biochemistry/Biophysics, Texas A&M University, MS 2128, College Station, TX 77845, USA

Received 13 April 2011; Revised 11 July 2011; Accepted 17 August 2011

Academic Editor: Shuyuan Yeh

Copyright © 2011 Brent W. Ferguson and Sumana Datta. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Heparan-sulfate proteoglycans (HSPGs) are required for maximal growth factor signaling in prostate cancer progression. The degree of sulfate modification on the covalently attached heparan sulfate (HS) chains is one of the determining factors of growth factor-HSPG interactions. Sulfate groups are transferred to HS chains via a series of O-sulfotransferases. In the present study, we demonstrate that Heparan sulfate 2-O-sulfotransferase (2OST) is essential for maximal proliferation and invasion of prostate cancer cells in the LNCaP-C4-2B model. We also show that a decrease in invasion due to 2OST siRNA is associated with an increase in actin and E-cadherin accumulation at the cell surface. 2OST expression correlates with increasing metastatic potential in this model. We demonstrate that 2OST expression is upregulated by the stress-inducible transcription factors HIF1α, ATF2, and NFκB. Chromatin immunoprecipitation analysis suggests that HIF1α and ATF2 act directly on the 2OST promoter, while NFκB acts indirectly.