Deletion of laminin-8 results in increased tumor neovascularization and metastasis in mice.
Laminin-8 (alpha 4 beta 1 gamma 1) is one of the major laminin isoforms expressed in vascular endothelial basement membranes. Here we show that deletion of laminin-8 in mice affects angiogenesis under pathological conditions. Murine tumor models used in laminin alpha 4-deficient mice results in hyperneovascularization and significant promotion of tumor growth and metastasis. The higher tumor growth rates in mutant mice correlate with decreased tumor cell apoptosis. Depletion of laminin alpha 4 chain may alter the structure of vascular basement membranes, leading to increased angiogenesis. Our data suggest that the laminin-8 plays a critical role in the regulation of pathological angiogenesis.
Zhou
Zhongjun
Z
Department of Biochemistry, Faculty of Medicine, University of Hong Kong, People's Republic of China. zhongjun@hkucc.hku.hk
Doi
Masayuki
M
Wang
Jianming
J
Cao
Renhai
R
Liu
Baohua
B
Chan
Kui Ming
KM
Kortesmaa
Jarkko
J
Sorokin
Lydia
L
Cao
Yihai
Y
Tryggvason
Karl
K
D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D002455:Cell Division / Q000502:physiology; D007797:Laminin / Q000096:biosynthesis / Q000172:deficiency* / Q000235:genetics; D008546:Melanoma, Experimental / Q000098:blood supply* / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D009362:Neoplasm Metastasis; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology
D007797:Laminin; C110308:laminin 8; C097043:laminin alpha5