Integrin α2 Mediates Selective Metastasis to the Liver
| Autor: | Norio Iizuka, Jesse W. Keller, Kelly Olino, Yukihiko Kato, Masaaki Oka, Fumin Chang, Lewis H. Romer, Shoichi Hazama, Kristen Meckel, Richard D. Schulick, Drew M. Pardoll, Jang-June Park, Christine A. Iacobuzio-Donahue, John M. Thompson, Kiyoshi Yoshimura, Ryouichi Tsunedomi, Lindsay S. Laird, Ajay N. Jain, Toshio Harada, Christina Y. Chia |
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| Jazyk: | angličtina |
| Rok vydání: | 2009 |
| Předmět: |
Collagen Type IV
Cancer Research Pathology medicine.medical_specialty Integrin Integrin alpha2 Melanoma Experimental Biology Article Antibodies Metastasis Focal adhesion Mice Liver Neoplasms Experimental medicine Animals Humans Mice Inbred BALB C Cell adhesion molecule Melanoma Liver Neoplasms Cancer medicine.disease Flow Cytometry Mice Inbred C57BL Oncology Focal Adhesion Kinase 1 Cancer research biology.protein Ectopic expression Female Colorectal Neoplasms |
| Popis: | 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. [Cancer Res 2009;69(18):7320–8] |
| Databáze: | OpenAIRE |
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