Endocan expression and localization in human glioblastomas.
Glioblastomas (GBMs) are highly malignant tumors characterized by microvascular proliferation and the pseudopalisading pattern of necrosis. Investigations have, therefore, focused on vascular and endothelial cell biology in GBM. Endocan, also called endothelial cell-specific molecule-1, is a proteoglycan that is secreted by endothelial cells and upregulated by proangiogenic factors. We found that endocan is not only expressed in vitro by endothelial cells but also in the T98G and U118MG human GBM cell lines. In U118MG cells, tumor necrosis factor and fibroblast growth factor 2 upregulated endocan production, whereas exposure to hypoxia or cobalt chloride, an inducer of hypoxia inducible factor 1, increased endocan release without affecting cell viability. Endocan expression in 82 brain tumors was studied by immunohistochemistry. Endocan immunoreactivity was detected in hyperplastic endothelial cells in high-grade gliomas, mostly at the tumor margins; endothelial cells were mostly endocan negative in low-grade gliomas, and it was never detected in the cerebral cortex distant from the tumors. Tumor cells in high-grade but not low-grade gliomas also expressed endocan, and it was detected in palisading cells surrounding areas of necrosis in GBM. Endothelial cell endocan immunoreactivity also correlated with shorter survival in glioma patients. Taken together, these results suggest that endocan is associated with abnormal vasculature in high-grade gliomas.
Maurage
Claude-Alain
CA
Institut National de la Santé et de la Recherche Médicale U837, JP Aubert Research Center and Département d'Histologie, Faculté de Médecine Henri Warembourg, Université de Lille II.
Adam
Estelle
E
Minéo
Jean-Francois
JF
Sarrazin
Stéphane
S
Debunne
Manuelle
M
Siminski
Rose-Mary
RM
Baroncini
Marc
M
Lassalle
Philippe
P
Blond
Serge
S
Delehedde
Maryse
M
D000328:Adult; D000368:Aged; D001932:Brain Neoplasms / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D045744:Cell Line, Tumor; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology*; D005909:Glioblastoma / Q000145:classification / Q000378:metabolism* / Q000401:mortality; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000378:metabolism*; D011509:Proteoglycans / Q000378:metabolism*; D016019:Survival Analysis; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
C101134:ESM1 protein, human; D009363:Neoplasm Proteins; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha