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

doi:10.1158/0008-5472.CAN-09-0315

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

Research output: Contribution to journal › Article › peer-review

56 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 language	English (US)
Pages (from-to)	7320-7328
Number of pages	9
Journal	Cancer Research
Volume	69
Issue number	18
DOIs	https://doi.org/10.1158/0008-5472.CAN-09-0315
State	Published - 2009
Externally published	Yes

ASJC Scopus subject areas

Oncology
Cancer Research

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10.1158/0008-5472.CAN-09-0315

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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

Yoshimura, K, Meckel, KF, Laird, LS, Chia, CY, Park, JJ, Olino, KL, Tsunedomi, R, Harada, T, Iizuka, N, Hazama, S, Kato, Y, Keller, JW, Thompson, JM, Chang, F, Romer, LH, Jain, A, Iacobuzio-Donahue, C, Oka, M, Pardoll, DM & Schulick, RD 2009, 'Integrin α2 mediates selective metastasis to the liver', Cancer Research, vol. 69, no. 18, pp. 7320-7328. https://doi.org/10.1158/0008-5472.CAN-09-0315

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title = "Integrin α2 mediates selective metastasis to the liver",

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.",

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

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doi = "10.1158/0008-5472.CAN-09-0315",

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AU - Olino, Kelly L.

AU - Tsunedomi, Ryouichi

AU - Harada, Toshio

AU - Iizuka, Norio

AU - Hazama, Shoichi

AU - Kato, Yukihiko

AU - Keller, Jesse W.

AU - Thompson, John M.

AU - Chang, Fumin

AU - Romer, Lewis H.

AU - Jain, Ajay

AU - Iacobuzio-Donahue, Christine

AU - Oka, Masaaki

AU - Pardoll, Drew M.

AU - Schulick, Richard D.

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Y1 - 2009

N2 - 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.

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Integrin α2 mediates selective metastasis to the liver

Abstract

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