Abstract B20: Secreted Protein Acidic and Rich in Cysteines-Like 1 Suppresses Aggressiveness and Predicts Better Survival in Colorectal Cancers

Abstract Background: 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. Material and Methods: Stable SPARCL1 transfectants, RKO-SPRCL1, 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 employed for survival analysis. The association of SPARCL1 with MET was sought by RT-PCR and Western blot analysis. Results: The ectopic expression of SPARCL1 significantly reduced the potential for anchorage-independent growth, migration and invasion, and it induced cell differentiation in RKO and SW620 cells. In mouse xenograft model, the expression of SPARCL1 significantly reduced the liver metastasis (P = 0.001). The patient-based studies revealed that the expression of SPARCL1 was related to better differentiation (P < 0.01), less lymph node involvement (Odds Ratio, OR=0.67, 95% CI 0.45-1.00) and less distant metastasis (OR=0.38, 95% CI 0.18-0.79). The Kaplan-Meier and COX analysis demonstrated that the expression of SPARCL1 was associated with better overall survival (Log–rank P < 0.01; hazard ratio, 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 CRC. Citation Format: Hu Hanguang, Zhang Hang, Ge Weiting, Liu Xiyong, Peng Jiaping, Yu Shujing, Yen Yun, Zheng Shu. Secreted protein acidic and rich in cysteines-like 1 suppresses aggressiveness and predicts better survival in colorectal cancers. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr B20.