title: Individual rac GTPases mediate aspects of prostate cancer cell and bone marrow endothelial cell interactions.
abstract: 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.
authors.affiliation: The Laboratory for Cytoskeletal Physiology, Department of Biological Science, University of Delaware, Newark, DE 19716, USA.
authors.forename: Moumita
authors.initials: M
authors.lastname: Chatterjee
authors.forename: Linda
authors.initials: L
authors.lastname: Sequeira
authors.forename: Mashariki
authors.initials: M
authors.lastname: Jenkins-Kabaila
authors.forename: Cara W
authors.initials: CW
authors.lastname: Dubyk
authors.forename: Surabhi
authors.initials: S
authors.lastname: Pathak
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: van Golen