CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase Rac.
Nearly 85% of the men who will die of prostate cancer (PCa) have skeletal metastases present. The ability of PCa cells to interact with the microenvironment determines the success of the tumor cell to form metastatic lesions. The ability to bind to human bone marrow endothelial (HBME) cells and undergo transendothelial cell migration are key steps in allowing the PCa cell to extravasate from the bone microvasculature and invade the bone stroma. We have previously demonstrated that monoctyte chemoattractant protein 1 (MCP-1; CCL2) is expressed by HBME cells and promotes PCa proliferation and migration. In the current study, we demonstrate that the CCL2 stimulation of PCa cells activates the small GTPase, Rac through the actin-associated protein PCNT1. Activation of Rac GTPase is accompanied by morphologic changes and the ability of the cells to undergo diapedesis through HBME cells. These data suggest a role for HBME-secreted CCL2 in promoting PCa cell extravasation into the bone microenvironment.
van Golen
Kenneth L
KL
Department of Biological Science, Laboratory of Cytoskeletal Physiology, University of Delaware, Newark, Delaware, USA.
Ying
Chi
C
Sequeira
Linda
L
Dubyk
Cara W
CW
Reisenberger
Tracy
T
Chinnaiyan
Arul M
AM
Pienta
Kenneth J
KJ
Loberg
Robert D
RD
D000199:Actins / Q000378:metabolism; D001859:Bone Neoplasms / Q000556:secondary; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D018932:Chemokine CCL2 / Q000494:pharmacology*; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D042783:Endothelial Cells / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology*; D004789:Enzyme Activation / Q000187:drug effects; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008297:Male; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D020744:rac GTP-Binding Proteins / Q000378:metabolism*
D000199:Actins; D018932:Chemokine CCL2; C503214:NUP85 protein, human; D009363:Neoplasm Proteins; D028861:Nuclear Pore Complex Proteins; D020744:rac GTP-Binding Proteins