title: Integrin alpha2 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 alpha2. The direct role of integrin alpha2 in hepatic metastasis was shown by comparison of high versus low-expressing populations, antibody blockade, and ectopic expression. Integrin alpha2-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 alpha2 expression contributes to liver metastasis in human colorectal cancer. These findings define integrin alpha2 as a molecule conferring selective potential for formation of hepatic metastasis, as well as a possible target to prevent their formation.
authors.affiliation: Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Blalock 685, Baltimore, MD 21287, USA.
authors.forename: Kiyoshi
authors.initials: K
authors.lastname: Yoshimura
authors.forename: Kristen F
authors.initials: KF
authors.lastname: Meckel
authors.forename: Lindsay S
authors.initials: LS
authors.lastname: Laird
authors.forename: Christina Y
authors.initials: CY
authors.lastname: Chia
authors.forename: Jang-June
authors.initials: JJ
authors.lastname: Park
authors.forename: Kelly L
authors.initials: KL
authors.lastname: Olino
authors.forename: Ryouichi
authors.initials: R
authors.lastname: Tsunedomi
authors.forename: Toshio
authors.initials: T
authors.lastname: Harada
authors.forename: Norio
authors.initials: N
authors.lastname: Iizuka
authors.forename: Shoichi
authors.initials: S
authors.lastname: Hazama
authors.forename: Yukihiko
authors.initials: Y
authors.lastname: Kato
authors.forename: Jesse W
authors.initials: JW
authors.lastname: Keller
authors.forename: John M
authors.initials: JM
authors.lastname: Thompson
authors.forename: Fumin
authors.initials: F
authors.lastname: Chang
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Romer
authors.forename: Ajay
authors.initials: A
authors.lastname: Jain
authors.forename: Christine
authors.initials: C
authors.lastname: Iacobuzio-Donahue
authors.forename: Masaaki
authors.initials: M
authors.lastname: Oka
authors.forename: Drew M
authors.initials: DM
authors.lastname: Pardoll
authors.forename: Richard D
authors.initials: RD
authors.lastname: Schulick
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D024141:Collagen Type IV / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000276:immunology / Q000473:pathology*; D005260:Female; D005434:Flow Cytometry; D051417:Focal Adhesion Kinase 1 / Q000378:metabolism; D006801:Humans; D039421:Integrin alpha2 / Q000096:biosynthesis* / Q000276:immunology; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000556:secondary*; D008114:Liver Neoplasms, Experimental / Q000276:immunology / Q000378:metabolism / Q000556:secondary; D008546:Melanoma, Experimental / Q000276:immunology / Q000473:pathology / Q000556:secondary*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL
chemical_list: D000906:Antibodies; D024141:Collagen Type IV; D039421:Integrin alpha2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse