Targeted Disruption of Endothelial Cell-selective Adhesion Molecule Inhibits Angiogenic Processes in Vitro and in Vivo

• Published in: The Journal of biological chemistry Vol. 278; no. 36; pp. 34598 - 34604
• Main Authors: Ishida, Tatsuro, Kundu, Ramendra K., Yang, Eugene, Hirata, Ken-ichi, Ho, Yen-Dong, Quertermous, Thomas
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 05.09.2003; American Society for Biochemistry and Molecular Biology
• Subjects: Animals; Biocompatible Materials - pharmacology; Cell Adhesion; Cell Adhesion Molecules - chemistry; Cell Adhesion Molecules - genetics; Cell Movement; Cloning, Molecular; Collagen - pharmacology; DNA, Complementary - metabolism; Drug Combinations; Endothelium - cytology; Fibroblast Growth Factor 2 - metabolism; Fluorescein - pharmacology; Gene Deletion; Laminin - pharmacology; Melanoma, Experimental; Mice; Mice, Transgenic; Microscopy, Fluorescence; Models, Genetic; Neoplasm Transplantation; Neovascularization, Pathologic; Platelet Endothelial Cell Adhesion Molecule-1 - biosynthesis; Protein Binding; Proteoglycans - pharmacology; Time Factors; Tumor Cells, Cultured
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.M304890200

Endothelial cell-selective adhesion molecule (ESAM) is a member of the immunoglobulin receptor family that mediates homophilic interactions between endothelial cells. To address potential in vivo angiogenic functions of this molecule, mice lacking ESAM (ESAM–/–) were generated by gene-targeted deletion. ESAM–/– mice did not show overt morphological defects in the vasculature. To evaluate the role of ESAM in pathological angiogenesis, wild type (WT) and ESAM–/– mice were injected with melanoma and Lewis lung carcinoma cells. By 14 days after injection, tumor volumes of B16F10 and LL/2 in ESAM–/– mice were 48 and 37% smaller, respectively, compared with WT mice. Vascular density of the tumors, as determined by CD31 staining, was also decreased in the ESAM null animals. Matrigel plug assays showed less neovascularization in ESAM–/– mice than in WT mice. ESAM–/– endothelial cells exhibited less in vitro tube formation and decreased migration in response to basic fibroblast growth factor when compared with WT cells, and endothelial-like yolk sac cells engineered to overexpress ESAM showed accelerated tube formation in vitro. These in vitro and in vivo studies suggest that ESAM has a redundant functional role in physiological angiogenesis but serves a unique and essential role in pathological angiogenic processes such as tumor growth.