Integrin alpha2 mediates selective metastasis to the liver.
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.
Yoshimura
Kiyoshi
K
Department of Surgery, Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins Medical Institutions, 600 North Wolfe Street, Blalock 685, Baltimore, MD 21287, USA.
Meckel
Kristen F
KF
Laird
Lindsay S
LS
Chia
Christina Y
CY
Park
Jang-June
JJ
Olino
Kelly L
KL
Tsunedomi
Ryouichi
R
Harada
Toshio
T
Iizuka
Norio
N
Hazama
Shoichi
S
Kato
Yukihiko
Y
Keller
Jesse W
JW
Thompson
John M
JM
Chang
Fumin
F
Romer
Lewis H
LH
Jain
Ajay
A
Iacobuzio-Donahue
Christine
C
Oka
Masaaki
M
Pardoll
Drew M
DM
Schulick
Richard D
RD
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
D000906:Antibodies; D024141:Collagen Type IV; D039421:Integrin alpha2; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse