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.
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Authors | 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 |
Journal | Clinical cancer research : an official journal of the American Association for Cancer Research
(Clin Cancer Res)
Vol. 18
Issue 19
Pg. 5438-48
(Oct 01 2012)
ISSN: 1557-3265 [Electronic] United States |
PMID | 22891198
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Chemical References |
- Calcium-Binding Proteins
- Extracellular Matrix Proteins
- SPARCL1 protein, human
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Topics |
- Animals
- Calcium-Binding Proteins
(genetics, metabolism)
- Cell Line, Tumor
- Cell Movement
(genetics)
- Colorectal Neoplasms
(genetics, metabolism, pathology)
- Epithelial-Mesenchymal Transition
- Extracellular Matrix Proteins
(genetics, metabolism)
- Gene Expression Regulation, Neoplastic
- Humans
- Kaplan-Meier Estimate
- Liver Neoplasms
(metabolism, pathology, secondary)
- Mice
- Mice, Nude
- Neoplasm Invasiveness
(pathology)
- Proportional Hazards Models
- Transplantation, Heterologous
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