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Deletion of Laminin-8 Results in Increased Tumor Neovascularization and Metastasis in Mice

¹ Department of Biochemistry, Faculty of Medicine, University of Hong Kong, Hong Kong; ² Division of Matrix Biology, Department of Biochemistry and Biophysics, and ³ Laboratory of Angiogenesis Research, Microbiology and Tumor Biology Center, Karolinska Institute, Stockholm, Sweden; ⁴ Institute of Molecular Medicine, Department of Medicine, University of California at San Diego, La Jolla, California; and ⁵ Lund University, Experimental Pathology, Lund, Sweden

Laminin-8 (4ß11) 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 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 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.

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