Secreted Protein Acidic and Rich in Cysteines-like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers
Secreted Protein Acidic and Rich in Cysteines-like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers
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富含半胱氨酸样 1 的酸性分泌蛋白可抑制攻击性并预测结直肠癌的更好生存率
DOI：
10.1158/1078-0432.ccr-12-0124
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发表时间：
2012-10-01
影响因子：
11.5
通讯作者：
Zheng, Shu
中科院分区：
文献类型：
--
作者：
Hu, Hanguang;Zhang, Hang;Zheng, Shu
目的：SPARCL 1是一种具有抑癌作用的细胞外基质糖蛋白。研究了SPARCL 1降低癌症侵袭性并预测结直肠癌（CRC）更好的存活率的假设。实验设计：构建稳定的SPARCL 1转染子RKO-SPARCL 1和相应的载体对照，并将其植入裸鼠中以产生肝转移的小鼠异种移植物模型。此外，对COH集（222个CRC）和ZJU集（412个CRC）进行了回顾性结局研究。免疫组化法检测SPARCL 1蛋白表达水平。生存分析采用Kaplan-Meier和考克斯分析。采用逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法（Western blot）检测SPARCL 1与间质上皮转化（MET）的关系。结果如下：SPARCL 1的异位表达显著降低了RKO和SW 620细胞的锚定非依赖性生长、迁移、侵袭和诱导细胞分化的潜力。在小鼠移植瘤模型中，SPARCL 1的表达显著降低肝转移（P < 0.01）。以患者为基础的研究显示，SPARCL 1的表达与分化程度高（P < 0.01）、淋巴结转移少（OR为0.67; 95% CI为0.45-1.00）、远处转移少（OR为0.38; 95% CI为0.18-0.79）有关。Kaplan-Meier和考克斯分析显示SPARCL 1的表达与较好的总生存率相关（log-rank：P < 0.01; HR，0.57; 95% CI，0.39-0.84）。转染SPARCL 1诱导结肠癌细胞的MET。结论：SPARCL 1可能通过MET促进CRCs分化，抑制CRCs的侵袭性。临床癌症研究; 18（19）; 5438-48。©2012 AACR。
Purpose: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is an extracellular matrix glycoprotein with malignancy-suppressing potential. The hypothesis that SPARCL1 reduces cancer invasiveness and predicts better survival in colorectal cancers (CRC) was investigated. Experimental Design: Stable SPARCL1 transfectants, RKO-SPARCL1, and corresponding vector control were constructed and implanted into nude mice to generate a mouse xenograft model of liver metastasis. Also, a retrospective outcome study was conducted on the COH set (222 CRCs) and ZJU set (412 CRCs). The protein expression level of SPARCL1 was determined by immunohistochemistry. The Kaplan–Meier and Cox analyses were used for survival analysis. The association of SPARCL1 with mesenchymal–epithelial transition (MET) was examined by reverse transcription PCR (RT-PCR) and Western blot analysis. Results: The ectopic expression of SPARCL1 significantly reduced the potential for anchorage-independent growth, migration, invasion and induced cell differentiation in RKO and SW620 cells. In mouse xenograft model, the expression of SPARCL1 significantly reduced the liver metastasis (P < 0.01). The patient-based studies revealed that the expression of SPARCL1 was related to better differentiation (P < 0.01), less lymph node involvement [OR, 0.67; 95% confidence interval (CI), 0.45–1.00], and less distant metastasis (OR, 0.38; 95% CI, 0.18–0.79). The Kaplan–Meier and Cox analysis showed that the expression of SPARCL1 was associated with better overall survival (log-rank: P < 0.01; HR, 0.57; 95% CI, 0.39–0.84). Transfection of SPARCL1 induced MET of colon cancer cells. Conclusion: SPARCL1 functions as a tumor suppressor promoting differentiation possibly via MET, which inhibits the aggressiveness of CRCs. Clin Cancer Res; 18(19); 5438–48. ©2012 AACR.