机构:[1]Department of Gastrointestinal Surgery, West China Hospital, SichuanUniversity, Chengdu 610041, Sichuan, China四川大学华西医院[2]Department of Pathology, WestChina Hospital, Sichuan University, Chengdu 610041, Sichuan, China[3]StateKey Laboratory of Biotherapy and Cancer Center/Collaborative InnovationCenter for Biotherapy, West China Hospital, Sichuan University, Chengdu610041, Sichuan, China四川大学华西医院[4]Institute of Digestive Surgery and State KeyLaboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu610041, Sichuan, China四川大学华西医院
Malignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far.
Profiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo.
SPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P < 0.05). Moreover, results of the Cox analysis showed that expression of SPARCL1 is an independent prognostic predictors for gastric GIST (P = 0.008; HR 0.157, 95% CI 0.040~ 0.612). Downregulation of SPARCL1 promoted cell migration and invasion, but did not affect proliferation, cell cycle and apoptosis of GIST 882 cells. In mouse xenograft model, GIST cells with the decreased expression of SPARCL1 presented an enhanced ability of liver metastasis (P < 0.05).
Taken together, our present study demonstrated that SPARCL1 have a certain degree of malignancy-suppressing potential through inhibiting the metastasis of gastric GIST.
基金:
National Natural Science Foundation of
China (no. 81572931).
语种:
外文
PubmedID:
中科院(CAS)分区:
出版当年[2018]版:
大类|3 区医学
小类|4 区胃肠肝病学
最新[2023]版:
大类|3 区医学
小类|4 区胃肠肝病学
第一作者:
第一作者机构:[1]Department of Gastrointestinal Surgery, West China Hospital, SichuanUniversity, Chengdu 610041, Sichuan, China
共同第一作者:
通讯作者:
推荐引用方式(GB/T 7714):
Chaoyong Shen,Yuan Yin,Huijiao Chen,et al.Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors.[J].BMC gastroenterology.2018,18(1):105.doi:10.1186/s12876-018-0833-8.
APA:
Chaoyong Shen,Yuan Yin,Huijiao Chen,Ruixue Wang,Xiaonan Yin...&Zongguang Zhou.(2018).Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors..BMC gastroenterology,18,(1)
MLA:
Chaoyong Shen,et al."Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors.".BMC gastroenterology 18..1(2018):105