Shen Chaoyong, Yin Yuan, Chen Huijiao, Wang Ruixue, Yin Xiaonan, Cai Zhaolun, Zhang Bo, Chen Zhixin, Zhou Zongguang
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
BMC Gastroenterol. 2018 Jul 4;18(1):105. doi: 10.1186/s12876-018-0833-8.
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.
胃肠道间质瘤（GIST）患者即使在治疗过程中也会出现恶性生长和转移，但其分子水平的机制至今仍知之甚少。
采用蛋白质芯片分析技术探索胃GIST组织中的蛋白质表达谱，通过RT-qPCR、蛋白质免疫印迹法和免疫组织化学法验证富含半胱氨酸样酸性分泌蛋白1（SPARCL1）的下调情况。研究特异性shRNA诱导的SPARCL1下调对GIST 882细胞生物学特性的影响。然后利用小鼠异种移植模型研究SPARCL1低表达是否影响GIST细胞在体内的转移能力。
与低级别恶性胃GIST相比，高级别恶性胃GIST中SPARCL1显著下调，其表达与肿瘤大小、有丝分裂指数、初诊时远处转移及GIST肿瘤进展密切相关（P<0.05）。此外，Cox分析结果显示，SPARCL1表达是胃GIST的独立预后预测指标（P=0.008；HR 0.157，95%CI 0.040~0.6仁）。SPARCL1下调促进GIST 882细胞迁移和侵袭，但不影响其增殖、细胞周期和凋亡。在小鼠异种移植模型中，SPARCL1表达降低的GIST细胞肝转移能力增强（P<0.05）。
综上所述，本研究表明SPARCL1通过抑制胃GIST转移具有一定程度的恶性抑制潜能。
