Published online before print January 17, 2008

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(American Journal of Pathology. 2008;172:545-553.)
© 2008 American Society for Investigative Pathology
DOI: 10.2353/ajpath.2008.070938

The Galectin Profile of the Endothelium

Altered Expression and Localization in Activated and Tumor Endothelial Cells

From the Angiogenesis Laboratory Maastricht, Department of Pathology, GROW School for Oncology and Developmental Biology, University Maastricht, The Netherlands

We previously identified overexpression of galectin-1 in activated tumor endothelium. Currently, the tumor vasculature is a target for therapeutic approaches. Little is known about galectin expression and regulation in the tumor vasculature. Here, we report the expression of galectin-1/-3/-8/-9 in the endothelium as determined by quantitative PCR, Western blot, flow cytometry, and immunohistochemistry. Galectin-2/-4/-12 were detectable at the mRNA level, albeit very low. Galectin-8 and -9 displayed alternative splicing. Immunohistochemistry of normal tissues revealed a broad but low expression of galectin-1 in the vasculature, whereas the expression levels and localization of the other galectins varied. Endothelial cell activation in vitro significantly increased the expression of galectin-1 (5.32 ± 1.97; P = 0.04) and decreased the expression of both galectin-8 (0.59 ± 0.12; P < 0.04) and galectin-9 (0.32 ± 0.06; P < 0.002). Galectin-3 expression was unaltered. Although a portion of these proteins is expressed intracellularly, the membrane protein level of galectin-1/-8/-9 was significantly increased on cell activation in vitro, 6-fold (P = 0.005), 3-fold (P = 0.002), and 1.4-fold (P = 0.04), respectively. Altered expression levels and cellular localization was also observed in vivo in the endothelium of human tumor tissue compared with normal tissue. These data show that endothelial cells express several members of the galectin family and that their expression and distribution changes on cell activation, resulting in a different profile in the tumor vasculature. This offers opportunities to develop therapeutic strategies that are independent of tumor type.

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