TY - JOUR
T1 - Expression of CD44v3 protein in human endothelial cells in vitro and in tumoral microvessels in vivo
AU - Forster-Horváth, C.
AU - Mészáros, L.
AU - Rásó, E.
AU - Döme, B.
AU - Ladányi, A.
AU - Morini, M.
AU - Albini, A.
AU - Tímár, J.
PY - 2004/9
Y1 - 2004/9
N2 - The most universal angiogenic cytokines (VEGF, bFGF, HGF) are all heparin-binding proteins, the function of which is dependent on cell surface heparan sulfate proteoglycans (HSPG). Several proteoglycans have been demonstrated in endothelial cells, but only glypican-1 from the cell surface HSPG subfamily was documented at protein level. Here, we show that CD44v3 is expressed in human immortalized endothelial cells [anchorage-dependent human umbilical vein endothelial cells (HUVEC) and anchorage-independent Kaposi sarcoma (KS-Imm)] at mRNA and protein level, but is absent from the primary culture of human brain microvascular endothelial cells. We have shown that CD44v3 has a large cytoplasmic pool in endothelial cells, but a limited surface expression, mainly at filopodia, colocalized with MMP-2. Angiogenic factors like VEGF or bFGF did not affect surface detection of CD44v3 suggesting a constitutive expression. The putative functional role for endothelial cell surface CD44v3 was identified in chemotaxis assay when anti-CD44v3 antibody pretreatment proved to be inhibitory for HUVEC. Furthermore, we provided evidence for the CD44v3 protein expression in human endothelial cells in vivo in peritumoral microvessels of both human melanoma and glottic cancers, suggesting a role for this part-time heparan sulfate proteoglycan in tumor induced angiogenesis.
AB - The most universal angiogenic cytokines (VEGF, bFGF, HGF) are all heparin-binding proteins, the function of which is dependent on cell surface heparan sulfate proteoglycans (HSPG). Several proteoglycans have been demonstrated in endothelial cells, but only glypican-1 from the cell surface HSPG subfamily was documented at protein level. Here, we show that CD44v3 is expressed in human immortalized endothelial cells [anchorage-dependent human umbilical vein endothelial cells (HUVEC) and anchorage-independent Kaposi sarcoma (KS-Imm)] at mRNA and protein level, but is absent from the primary culture of human brain microvascular endothelial cells. We have shown that CD44v3 has a large cytoplasmic pool in endothelial cells, but a limited surface expression, mainly at filopodia, colocalized with MMP-2. Angiogenic factors like VEGF or bFGF did not affect surface detection of CD44v3 suggesting a constitutive expression. The putative functional role for endothelial cell surface CD44v3 was identified in chemotaxis assay when anti-CD44v3 antibody pretreatment proved to be inhibitory for HUVEC. Furthermore, we provided evidence for the CD44v3 protein expression in human endothelial cells in vivo in peritumoral microvessels of both human melanoma and glottic cancers, suggesting a role for this part-time heparan sulfate proteoglycan in tumor induced angiogenesis.
KW - CD44v3
KW - Microvessels
KW - Proteoglycan
UR - http://www.scopus.com/inward/record.url?scp=4143136353&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=4143136353&partnerID=8YFLogxK
U2 - 10.1016/j.mvr.2004.05.001
DO - 10.1016/j.mvr.2004.05.001
M3 - Article
C2 - 15313120
AN - SCOPUS:4143136353
VL - 68
SP - 110
EP - 118
JO - Microvascular Research
JF - Microvascular Research
SN - 0026-2862
IS - 2
ER -