Connective tissue growth factor associated with oncogenic activities and drug resistance in glioblastoma multiforme |
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| Authors: | Dong Yin Weikai Chen James O'Kelly Daning Lu Michelle Ham Ngan B. Doan Dong Xie Charles Wang Jay Vadgama Jonathan W. Said Keith L. Black H. Phillip Koeffler |
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| Affiliation: | 1. Department of Pathology, Shantou University Medical College, Guangdong, China;2. Division of Hematology/Oncology, Cedars‐Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA;3. Tel.: +(310)‐423‐7740, Fax: +(310)‐423‐0225;4. Department of Pathology, UCLA School of Medicine, Los Angeles, CA;5. Institute for Nutritional Science, SIBS Chinese Academy of Science, Shanghai, China;6. Functional Genomics Core, Beckman Research Institute, City of Hope Comprehensive Cancer Center, Duarte, CA;7. Department of Medicine, David Geffen School of Medicine at UCLA, Los Angeles, CA;8. Department of Medicine, Charles R. Drew University of Medicine and Science, UCLA School of Medicine, Los Angeles, CA;9. Maxine Dunitz Neurosurgical Institute, Cedars‐Sinai Medical Center, UCLA School of Medicine, Los Angeles, CA;10. National Cancer Institute of Singapore, National University of Singapore |
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| Abstract: | ![]()
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. |
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| Keywords: | CTGF CCN drug resistance glioblastoma multiforme (GBM) |
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