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.