Table of Contents
Journal of Signal Transduction
Volume 2011, Article ID 541851, 13 pages
Research Article

Individual Rac GTPases Mediate Aspects of Prostate Cancer Cell and Bone Marrow Endothelial Cell Interactions

1The Laboratory for Cytoskeletal Physiology, Department of Biological Science, University of Delaware, Newark, DE 19716, USA
2The Center for Translational Cancer Research, University of Delaware, Newark, DE 19716, USA
3Biology Department, Lincoln University, Chester County, PA 19352, USA
4The Delaware Biotechnology Institute, University of Delaware, 320 Wolf Hall, Newark, DE 19716, USA

Received 1 November 2010; Revised 21 February 2011; Accepted 13 April 2011

Academic Editor: Adrienne D. Cox

Copyright © 2011 Moumita Chatterjee et al. 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.


The Rho GTPases organize the actin cytoskeleton and are involved in cancer metastasis. Previously, we demonstrated that RhoC GTPase was required for PC-3 prostate cancer cell invasion. Targeted down-regulation of RhoC led to sustained activation of Rac1 GTPase and morphological, molecular and phenotypic changes reminiscent of epithelial to mesenchymal transition. We also reported that Rac1 is required for PC-3 cell diapedesis across a bone marrow endothelial cell layer. In the current study, we queried whether Rac3 and RhoG GTPases also have a role in prostate tumor cell diapedesis. Using specific siRNAs we demonstrate roles for each protein in PC-3 and C4-2 cell adhesion and diapedesis. We have shown that the chemokine CCL2 induces tumor cell diapedesis via Rac1 activation. Here we find that RhoG partially contributes to CCL2-induced tumor cell diapedesis. We also find that Rac1 GTPase mediates tight binding of prostate cancer cells to bone marrow endothelial cells and promotes retraction of endothelial cells required for tumor cell diapedesis. Finally, Rac1 leads to β1 integrin activation, suggesting a mechanism that Rac1 can mediate tight binding with endothelial cells. Together, our data suggest that Rac1 GTPase is key mediator of prostate cancer cell-bone marrow endothelial cell interactions.