CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac

Kenneth L. Van Golen, Chi Ying, Linda Sequeira, Cara W. Dubyk, Tracy Reisenberger, Arul M. Chinnaiyan, Kenneth Pienta, Robert D. Loberg

Research output: Contribution to journalArticle

Abstract

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 celI 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.

Original languageEnglish (US)
Pages (from-to)1587-1597
Number of pages11
JournalJournal of Cellular Biochemistry
Volume104
Issue number5
DOIs
StatePublished - Aug 1 2008
Externally publishedYes

Fingerprint

Transendothelial and Transepithelial Migration
Monomeric GTP-Binding Proteins
Cell Movement
Prostatic Neoplasms
Bone
Chemical activation
Bone Marrow Cells
Endothelial cells
Endothelial Cells
Bone and Bones
GTP Phosphohydrolases
Chemotactic Factors
Microvessels
Actins
Proteins
Bone Marrow
Tumors
Neoplasm Metastasis
Neoplasms

Keywords

  • Actin cytoskeleton
  • Diapedesis
  • Metastasis
  • Monoctye chemoattractant protein 1

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

Cite this

Van Golen, K. L., Ying, C., Sequeira, L., Dubyk, C. W., Reisenberger, T., Chinnaiyan, A. M., ... Loberg, R. D. (2008). CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac. Journal of Cellular Biochemistry, 104(5), 1587-1597. https://doi.org/10.1002/jcb.21652

CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac. / Van Golen, Kenneth L.; Ying, Chi; Sequeira, Linda; Dubyk, Cara W.; Reisenberger, Tracy; Chinnaiyan, Arul M.; Pienta, Kenneth; Loberg, Robert D.

In: Journal of Cellular Biochemistry, Vol. 104, No. 5, 01.08.2008, p. 1587-1597.

Research output: Contribution to journalArticle

Van Golen, KL, Ying, C, Sequeira, L, Dubyk, CW, Reisenberger, T, Chinnaiyan, AM, Pienta, K & Loberg, RD 2008, 'CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac', Journal of Cellular Biochemistry, vol. 104, no. 5, pp. 1587-1597. https://doi.org/10.1002/jcb.21652
Van Golen KL, Ying C, Sequeira L, Dubyk CW, Reisenberger T, Chinnaiyan AM et al. CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac. Journal of Cellular Biochemistry. 2008 Aug 1;104(5):1587-1597. https://doi.org/10.1002/jcb.21652
Van Golen, Kenneth L. ; Ying, Chi ; Sequeira, Linda ; Dubyk, Cara W. ; Reisenberger, Tracy ; Chinnaiyan, Arul M. ; Pienta, Kenneth ; Loberg, Robert D. / CCL2 induces prostate cancer transendothelial cell migration via activation of the small GTPase rac. In: Journal of Cellular Biochemistry. 2008 ; Vol. 104, No. 5. pp. 1587-1597.
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AB - 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 celI 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.

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