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Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme
Author(s) -
Yin Dong,
Chen Weikai,
O'Kelly James,
Lu Daning,
Ham Michelle,
Doan Ngan B.,
Xie Dong,
Wang Charles,
Vadgama Jay,
Said Jonathan W.,
Black Keith L.,
Koeffler H. Phillip
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25257
Subject(s) - ctgf , cyr61 , cancer research , growth factor , angiogenesis , carcinogenesis , biology , glioma , proteasome inhibitor , connective tissue , pathology , medicine , cancer , immunology , receptor , multiple myeloma
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.