Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme.
Connective tissue growth factor (CTGF or CCN2) is a secreted protein that belongs to the CCN [cysteine-rich CYR61/CTGF/nephroblastoma-overexpressed gene] family. These proteins have been implicated in various biological processes, including stimulation of cell proliferation, migration, angiogenesis and tumorigenesis. In a previous study, we found that CTGF mRNA was elevated in primary gliomas, and a significant correlation existed between CTGF mRNA levels versus tumor grade, histology and patient survival. In this study, the role of CTGF in glioma tumorigenesis was explored. Forced expression of CTGF in glioblastoma multiforme (GBM) cells accelerated their growth in liquid culture and soft agar, stimulated cells migration in Boyden chamber assays and significantly increased their ability to form large, vascularized tumors in nude mice. CTGF induced the expression of the antiapoptotic proteins, Bcl-xl, Survivin and Flip. Overexpression of CTGF caused the U343 GBM cells to survive for longer than 40 days in serum-free medium and resist antitumor drugs including tumor necrosis factor (TNF), TNF-related apoptosis-inducing ligand, VELCADE (bortezomib, proteasome inhibitor) and temozolomide. Our data suggest that CTGF plays an important role in glioma progression, by supporting tumor cells survival and drug resistance.
Yin
Dong
D
Department of Pathology, Shantou University Medical College, Guangdong, China.
Chen
Weikai
W
O'Kelly
James
J
Lu
Daning
D
Ham
Michelle
M
Doan
Ngan B
NB
Xie
Dong
D
Wang
Charles
C
Vadgama
Jay
J
Said
Jonathan W
JW
Black
Keith L
KL
Koeffler
H Phillip
HP
D000818:Animals; D001932:Brain Neoplasms / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D002471:Cell Transformation, Neoplastic / Q000235:genetics; D055513:Connective Tissue Growth Factor / Q000235:genetics*; D016895:Culture Media, Serum-Free; D019008:Drug Resistance, Neoplasm; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D009389:Neovascularization, Pathologic / Q000235:genetics; D014162:Transfection
C526317:CCN2 protein, human; D016895:Culture Media, Serum-Free; D055513:Connective Tissue Growth Factor