TY - JOUR
T1 - The galectin profile of the endothelium
T2 - altered expression and localization in activated and tumor endothelial cells
AU - Thijssen, Victor L
AU - Hulsmans, Sarah
AU - Griffioen, Arjan W
PY - 2008/2
Y1 - 2008/2
N2 - 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.
AB - 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.
KW - Blotting, Western
KW - Colonic Neoplasms/metabolism
KW - DNA Primers
KW - Endothelium, Vascular/metabolism
KW - Flow Cytometry
KW - Galectins/biosynthesis
KW - Gene Expression
KW - Humans
KW - Immunohistochemistry
KW - Protein Isoforms/biosynthesis
KW - RNA, Messenger/analysis
KW - Reverse Transcriptase Polymerase Chain Reaction
U2 - 10.2353/ajpath.2008.070938
DO - 10.2353/ajpath.2008.070938
M3 - Article
C2 - 18202194
VL - 172
SP - 545
EP - 553
JO - The American Journal of Pathology
JF - The American Journal of Pathology
SN - 0002-9440
IS - 2
ER -