Secreted protein acidic and rich in cysteines-like 1 suppresses aggressiveness and predicts better survival in colorectal cancers

Hanguang Hu, Hang Zhang, Weiting Ge, Xiyong Liu, Sofia Loera, Peiguo Chu, Huarong Chen, Jiaping Peng, Lun Zhou, Shujing Yu, Ying Yuan, Suzhan Zhang, Lily Lai, Yun Yen, Shu Zheng

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27 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)5438-5448
Number of pages11
JournalClinical Cancer Research
Volume18
Issue number19
DOIs
Publication statusPublished - Oct 1 2012
Externally publishedYes

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Hu, H., Zhang, H., Ge, W., Liu, X., Loera, S., Chu, P., Chen, H., Peng, J., Zhou, L., Yu, S., Yuan, Y., Zhang, S., Lai, L., Yen, Y., & Zheng, S. (2012). Secreted protein acidic and rich in cysteines-like 1 suppresses aggressiveness and predicts better survival in colorectal cancers. Clinical Cancer Research, 18(19), 5438-5448. https://doi.org/10.1158/1078-0432.CCR-12-0124