CCL2 is a potent regulator of prostate cancer cell migration and proliferation

Robert D. Loberg, LaShon L. Day, Jason Harwood, Chi Ying, Lauren N. St. John, Ryan Giles, Chris K. Neeley, Kenneth Pienta

Research output: Contribution to journalArticle

Abstract

Tumor cells in the bone interact with the microenvironment to promote tumor cell survival and proliferation, resulting in a lethal phenotype for patients with advanced prostate cancer. Monocyte chemoattractant protein 1 (CCL2) is a member of the CC chemokine family and is known to promote monocyte chemotaxis to sites of inflammation. Here we have shown that human bone marrow endothelial (HBME) cells secrete significantly higher levels of CCL2 compared to human aortic endothelial cells and human dermal microvascular endothelial cells. Furthermore, we demonstrate that CCL2 is a potent chemoattractant of prostate cancer epithelial cells, and that stimulation of PC-3 and VCaP cells resulted in a dose-dependent activation of PI3 kinase/Akt signaling pathway. Activation of the PI3 kinase/Akt pathway was found to be vital to the proliferative effects of CCL2 stimulation of both PC-3 and VCaP cells. Additionally, CCL2 stimulated the phosphorylation of p70-S6 kinase (a downstream target of Akt) and induced actin rearrangement, resulting in a dynamic morphologic change indicative of microspike formation. These data suggest that bone marrow endothelial cells are a major source of CCL2, and that an elevated secretion of CCL2 recruits prostate cancer epithelial cells to the bone microenvironment and regulates their proliferation rate.

Original languageEnglish (US)
Pages (from-to)578-586
Number of pages9
JournalNeoplasia
Volume8
Issue number7
DOIs
StatePublished - 2006
Externally publishedYes

Fingerprint

Cell Movement
Prostatic Neoplasms
Endothelial Cells
Cell Proliferation
Phosphatidylinositol 3-Kinases
Bone Marrow Cells
Epithelial Cells
70-kDa Ribosomal Protein S6 Kinases
Bone and Bones
CC Chemokines
Chemokine CCL2
Chemotactic Factors
Chemotaxis
Actins
Monocytes
Neoplasms
Cell Survival
Phosphorylation
Inflammation
Phenotype

Keywords

  • CCL2
  • Chemokine
  • Metastasis
  • Migration
  • Prostate cancer

ASJC Scopus subject areas

  • Cancer Research

Cite this

Loberg, R. D., Day, L. L., Harwood, J., Ying, C., St. John, L. N., Giles, R., ... Pienta, K. (2006). CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia, 8(7), 578-586. https://doi.org/10.1593/neo.06280

CCL2 is a potent regulator of prostate cancer cell migration and proliferation. / Loberg, Robert D.; Day, LaShon L.; Harwood, Jason; Ying, Chi; St. John, Lauren N.; Giles, Ryan; Neeley, Chris K.; Pienta, Kenneth.

In: Neoplasia, Vol. 8, No. 7, 2006, p. 578-586.

Research output: Contribution to journalArticle

Loberg, RD, Day, LL, Harwood, J, Ying, C, St. John, LN, Giles, R, Neeley, CK & Pienta, K 2006, 'CCL2 is a potent regulator of prostate cancer cell migration and proliferation', Neoplasia, vol. 8, no. 7, pp. 578-586. https://doi.org/10.1593/neo.06280
Loberg RD, Day LL, Harwood J, Ying C, St. John LN, Giles R et al. CCL2 is a potent regulator of prostate cancer cell migration and proliferation. Neoplasia. 2006;8(7):578-586. https://doi.org/10.1593/neo.06280
Loberg, Robert D. ; Day, LaShon L. ; Harwood, Jason ; Ying, Chi ; St. John, Lauren N. ; Giles, Ryan ; Neeley, Chris K. ; Pienta, Kenneth. / CCL2 is a potent regulator of prostate cancer cell migration and proliferation. In: Neoplasia. 2006 ; Vol. 8, No. 7. pp. 578-586.
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