CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib.
CCBE1 promotes GIST development through enhancing angiogenesis and mediating resistance to imatinib.
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DOI：
10.1038/srep31071
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发表时间：
2016-08-10
影响因子：
4.6
通讯作者：
Zhang ZG
中科院分区：
文献类型：
--
作者：
Tian GA;Zhu CC;Zhang XX;Zhu L;Yang XM;Jiang SH;Li RK;Tu L;Wang Y;Zhuang C;He P;Li Q;Cao XY;Cao H;Zhang ZG
胃肠道间质瘤(GIST)是消化道最主要的间叶性肿瘤。到目前为止，甲磺酸伊马替尼一直被用作不能切除和转移的GIST患者的标准一线治疗方案，或用于接受手术切除的晚期GIST患者的辅助治疗。然而，对伊马替尼的继发性耐药通常会发生，这是GIST治疗成功的主要障碍。在本研究中，我们首次发现胶原和钙结合EGF结构域1(CCBE1)的表达随着NIH分级的危险程度而逐渐升高，CCBE1阳性患者预后不良。体外实验表明，重组CCBE1蛋白能促进血管生成，并中和伊马替尼对GIST-T1细胞的部分作用。综上所述，这些数据表明CCBE1可作为GIST术后患者预后的一个新的预测指标，并可能在促进GIST进展方面发挥重要作用。
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.