Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells

Takashi Murakami, Wusi Maki, Adela R. Cardones, Hui Fang, Adrian Tun Kyi, Frank O. Nestle, Samuel T Hwang

Research output: Contribution to journalArticle

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Abstract

The chemokine receptors CC chemokine receptor (CCR) 7 and CXC chemokine receptor (CXCR) 4 have been implicated in cancer metastasis. To evaluate whether CXCR4 is sufficient to increase tumor metastasis in an organ-specific manner, we transduced murine B16 melanoma cells with CXCR4 (CXCR4-B16) and followed the metastatic fate of the transduced cells in both i.v. and s.c. inoculation models of metastasis. CXCR4-B16 cells demonstrated marked increases (>10-fold) in pulmonary metastasis compared with vector (pLNCX2)-B16 after i.v. and s.c. inoculation of tumor cells. The increase in metastasis could be completely inhibited by T22, a small peptide antagonist of CXCR4. As early as 24 and 48 h after i.v. injection, CXCR4-B16 cells were significantly increased in the lung compared with control B16 cells by 5- and 10-fold (P < 0.05), respectively. CXCR4-B16 cells adhered better to both dermal and pulmonary microvascular endothelial cells relative to control B16 cells. Moreover, CXCL12 promoted the growth of CXCR4-B16 cells in vitro. Whereas expression of CXCR4 in B16 cells dramatically enhanced pulmonary metastasis, metastasis to the lymph nodes, liver, and kidney was rare. Immunohistochemical staining of both primary human cutaneous melanoma and pulmonary metastases revealed CXCR4 expression. Thus, CXCR4 plays a potentially important role in promoting organ-selective metastasis, possibly by stimulating tumor adhesion to microvascular endothelial cells and by enhancing the growth of tumor cells under stress.

Original languageEnglish (US)
Pages (from-to)7328-7334
Number of pages7
JournalCancer Research
Volume62
Issue number24
StatePublished - Dec 15 2002
Externally publishedYes

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CXCR4 Receptors
Experimental Melanomas
Lung
Neoplasm Metastasis
Neoplasms
CCR7 Receptors
Endothelial Cells
Skin
Chemokine Receptors
Growth
Melanoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Murakami, T., Maki, W., Cardones, A. R., Fang, H., Tun Kyi, A., Nestle, F. O., & Hwang, S. T. (2002). Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Research, 62(24), 7328-7334.

Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. / Murakami, Takashi; Maki, Wusi; Cardones, Adela R.; Fang, Hui; Tun Kyi, Adrian; Nestle, Frank O.; Hwang, Samuel T.

In: Cancer Research, Vol. 62, No. 24, 15.12.2002, p. 7328-7334.

Research output: Contribution to journalArticle

Murakami, T, Maki, W, Cardones, AR, Fang, H, Tun Kyi, A, Nestle, FO & Hwang, ST 2002, 'Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells', Cancer Research, vol. 62, no. 24, pp. 7328-7334.
Murakami T, Maki W, Cardones AR, Fang H, Tun Kyi A, Nestle FO et al. Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. Cancer Research. 2002 Dec 15;62(24):7328-7334.
Murakami, Takashi ; Maki, Wusi ; Cardones, Adela R. ; Fang, Hui ; Tun Kyi, Adrian ; Nestle, Frank O. ; Hwang, Samuel T. / Expression of CXC chemokine receptor-4 enhances the pulmonary metastatic potential of murine B16 melanoma cells. In: Cancer Research. 2002 ; Vol. 62, No. 24. pp. 7328-7334.
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