CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib

CCBE1 通过增强血管生成和介导对伊马替尼的耐药性来促进 GIST 的发展

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作者:Guang-Ang Tian, Chun-Chao Zhu, Xiao-Xin Zhang, Lei Zhu, Xiao-Mei Yang, Shu-Heng Jiang, Rong-Kun Li, Lin Tu, Yang Wang, Chun Zhuang, Ping He, Qing Li, Xiao-Yan Cao, Hui Cao, Zhi-Gang Zhang

Abstract

Gastrointestinal stromal tumor (GIST) is the most major mesenchymal neoplasm of the digestive tract. Up to now, imatinib mesylate has been used as a standard first-line treatment for irresectable and metastasized GIST patients or adjuvant treatment for advanced GIST patients who received surgical resection. However, secondary resistance to imatinib usually happens, resulting in a major obstacle in GIST successful therapy. In this study, we first found that collagen and calcium binding EGF domains 1 (CCBE1) expression gradually elevated along with the risk degree of NIH classification, and poor prognosis emerged in the CCBE1-positive patients. In vitro experiments showed that recombinant CCBE1 protein can enhance angiogenesis and neutralize partial effect of imatinib on the GIST-T1 cells. In conclusion, these data indicated that CCBE1 may be served as a new predictor of prognosis in post-operative GIST patients and may play an important role in stimulating GIST progression.

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