Integrin α2 mediates selective metastasis to the liver

Kiyoshi Yoshimura, Kristen F. Meckel, Lindsay S. Laird, Christina Y. Chia, Jang June Park, Kelly L. Olino, Ryouichi Tsunedomi, Toshio Harada, Norio Iizuka, Shoichi Hazama, Yukihiko Kato, Jesse W. Keller, John M. Thompson, Fumin Chang, Lewis H. Romer, Ajay Jain, Christine Iacobuzio-Donahue, Masaaki Oka, Drew M. Pardoll, Richard D. Schulick

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53 Scopus citations

Abstract

Cancers display distinct patterns of organ-specific metastasis. Comparative analysis of a broad array of cell membrane molecules on a liver-metastasizing subline of B16 melanoma versus the parental B16-F0 revealed unique up-regulation of integrin α2. The direct role of integrin α2 in hepatic metastasis was shown by comparison of high versus low-expressing populations, antibody blockade, and ectopic expression. Integrin α2-mediated binding to collagen type IV (highly exposed in the liver sinusoids) and collagen type IV-dependent activation of focal adhesion kinase are both known to be important in the metastatic process. Analysis of primary colorectal cancers as well as coexisting liver and lung metastases from individual patients suggests that integrin α2 expression contributes to liver metastasis in human colorectal cancer. These findings define integrin α2 as a molecule conferring selective potential for formation of hepatic metastasis, as well as a possible target to prevent their formation.

Original languageEnglish
Pages (from-to)7320-7328
Number of pages9
JournalCancer research
Volume69
Issue number18
DOIs
StatePublished - Oct 13 2009
Externally publishedYes

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    Yoshimura, K., Meckel, K. F., Laird, L. S., Chia, C. Y., Park, J. J., Olino, K. L., Tsunedomi, R., Harada, T., Iizuka, N., Hazama, S., Kato, Y., Keller, J. W., Thompson, J. M., Chang, F., Romer, L. H., Jain, A., Iacobuzio-Donahue, C., Oka, M., Pardoll, D. M., & Schulick, R. D. (2009). Integrin α2 mediates selective metastasis to the liver. Cancer research, 69(18), 7320-7328. https://doi.org/10.1158/0008-5472.CAN-09-0315