Journal
ONCOTARGET
Volume 6, Issue 29, Pages 27239-27251Publisher
IMPACT JOURNALS LLC
DOI: 10.18632/oncotarget.4835
Keywords
glioblastoma multiforme; anti-angiogenic therapy; bevacizumab-resistance; Talin1; patient derived xenograft models
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Funding
- Samsung Medical Center grant
- Korea Health Technology R&D Project through Korea Health Industry Development Institute (KHIDI) - Ministry of Health & Welfare, Republic of Korea [HI14C3418]
- Korea Health technology R&D Project, Ministry of Health & Welfare, Republic of Korea [A120446]
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Glioblastoma multiforme (GBM) possesses florid angiogenesis. However, the anti-angiogenic agent, Bevacizumab, did not improve overall survival of GBM patients. For more durable anti-angiogenic treatment, we interrogated resistant mechanisms of GBM against Bevacizumab. Serial orthotopic transplantation of in vivo Bevacizumab-treated GBM cells provoked complete refractoriness to the anti-angiogenic treatment. These tumors were also highly enriched with malignant phenotypes such as invasiveness, epithelial to mesenchymal transition, and stem-like features. Through transcriptome analysis, we identified that Talin1 (TLN1) significantly increased in the refractory GBMs. Inhibition of TLN1 not only attenuated malignant characteristics of GBM cells but also reversed the resistance to the Bevacizumab treatment. These data implicate TLN1 as a novel therapeutic target for GBM to overcome resistance to anti-angiogenic therapies.
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