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CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin.

Publication ,  Journal Article
Cardones, AR; Murakami, T; Hwang, ST
Published in: Cancer Res
October 15, 2003

The chemokine receptor, CXCR4, is expressed by human melanomas, and its ligand, CXCL12, is frequently produced at sites of melanoma metastasis. Herein, we examine CXCR4-enhanced binding of B16 murine melanoma cells to endothelial cells (ECs) and recombinant adhesion molecules in vitro to determine the role of tumor- and EC-derived adhesion molecules in tumor metastasis. By flow cytometry, unstimulated primary lung ECs showed constitutive expression of vascular cellular adhesion molecule 1 (VCAM-1), whereas skin-derived ECs did not. All B16 cell lines tested showed constitutive expression of alpha(4) and beta(1) integrin chains but showed no expression of beta(2) integrins. CXCR4-B16 arrest on VCAM-1/immunoglobulin-coated plates and tumor necrosis factor alpha-stimulated ECs under physiological shear stress conditions (1.5 dynes/cm(2)) was rapid, resistant to shear stress of 10 dynes/cm(2), and showed no evidence of rolling before arrest. In vitro, CXCR4-B16 cell binding to ECs was blocked by anti-beta(1) and anti-CXCL12 monoclonal antibodies. In vivo, metastasis of CXCR4-B16 cells to murine lungs was strongly inhibited by anti-CXCL12 and two different anti-beta(1) monoclonal antibodies. Finally, CXCR4-B16 exposed to CXCL12 rapidly increased binding affinity for soluble VCAM-1/immunoglobulin as detected by a flow cytometric assay. Thus, beta(1) integrins play a critical role in CXCR4-mediated B16 tumor cell metastasis in vivo and may be a potential target for inhibition of tumor metastasis, particularly to the lung.

Duke Scholars

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 15, 2003

Volume

63

Issue

20

Start / End Page

6751 / 6757

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Receptors, CXCR4
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C
  • Mice
  • Melanoma, Experimental
  • Lung Neoplasms
  • Integrin beta1
  • Female
  • Endothelium, Vascular
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Cardones, A. R., Murakami, T., & Hwang, S. T. (2003). CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin. Cancer Res, 63(20), 6751–6757.
Cardones, Adela R., Takashi Murakami, and Sam T. Hwang. “CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin.Cancer Res 63, no. 20 (October 15, 2003): 6751–57.
Cardones AR, Murakami T, Hwang ST. CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin. Cancer Res. 2003 Oct 15;63(20):6751–7.
Cardones, Adela R., et al. “CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin.Cancer Res, vol. 63, no. 20, Oct. 2003, pp. 6751–57.
Cardones AR, Murakami T, Hwang ST. CXCR4 enhances adhesion of B16 tumor cells to endothelial cells in vitro and in vivo via beta(1) integrin. Cancer Res. 2003 Oct 15;63(20):6751–6757.

Published In

Cancer Res

ISSN

0008-5472

Publication Date

October 15, 2003

Volume

63

Issue

20

Start / End Page

6751 / 6757

Location

United States

Related Subject Headings

  • Vascular Cell Adhesion Molecule-1
  • Receptors, CXCR4
  • Oncology & Carcinogenesis
  • Mice, Inbred BALB C
  • Mice
  • Melanoma, Experimental
  • Lung Neoplasms
  • Integrin beta1
  • Female
  • Endothelium, Vascular