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


METHODS
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.


CONCLUSIONS
SPARCL1 functions as a tumor suppressor promoting differentiation possibly via MET, which inhibits the aggressiveness of CRCs.
School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
Hanguang
H
Hu
Hang
H
Zhang
Weiting
W
Ge
Xiyong
X
Liu
Sofia
S
Loera
Peiguo
P
Chu
Huarong
H
Chen
Jiaping
J
Peng
Lun
L
Zhou
Shujing
S
Yu
Ying
Y
Yuan
Suzhan
S
Zhang
Lily
L
Lai
Yun
Y
Yen
Shu
S
Zheng
D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D058750:Epithelial-Mesenchymal Transition; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D009361:Neoplasm Invasiveness / Q000473:pathology; D016016:Proportional Hazards Models; D014183:Transplantation, Heterologous
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; C503126:SPARCL1 protein, human