Format

Send to

Choose Destination
BMC Gastroenterol. 2018 Jul 4;18(1):105. doi: 10.1186/s12876-018-0833-8.

Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors.

Author information

1
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
2
Department of Pathology, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
3
State Key Laboratory of Biotherapy and Cancer Center/Collaborative Innovation Center for Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China.
4
Department of Gastrointestinal Surgery, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. hxwcwk@126.com.
5
Institute of Digestive Surgery and State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, 610041, Sichuan, China. zhou767@163.com.

Abstract

BACKGROUND:

Malignant growth and metastasis of gastrointestinal stromal tumors (GIST) occur in some patients even during the course of treatment, but their mechanisms remains poorly understand at the molecular level so far.

METHODS:

Profiles of protein expression in gastric GIST tissues were explored using protein microarray analysis, down-regulation of SPARCL1 (secreted protein acidic and rich in cysteine-like protein 1) was validated by RT-qPCR, western blot and immunohistochemistry. The effect of specific shRNA-induced SPARCL1 downregulation on the biological traits of GIST 882 cell was investigated. We then employed a mouse xenograft model to investigate whether the low-expression of SPARCL1 impact the metastasis ability of GIST cells in vivo.

RESULTS:

SPARCL1 was significantly downregulated in the gastric GIST with high-grade malignance as compared with low-grade malignance, its expression was closely correlated with tumor size, mitotic index, distant metastasis at the time of initial diagnosis and tumor progression of GIST (P < 0.05). Moreover, results of the Cox analysis showed that expression of SPARCL1 is an independent prognostic predictors for gastric GIST (P = 0.008; HR 0.157, 95% CI 0.040~ 0.612). Downregulation of SPARCL1 promoted cell migration and invasion, but did not affect proliferation, cell cycle and apoptosis of GIST 882 cells. In mouse xenograft model, GIST cells with the decreased expression of SPARCL1 presented an enhanced ability of liver metastasis (P < 0.05).

CONCLUSIONS:

Taken together, our present study demonstrated that SPARCL1 have a certain degree of malignancy-suppressing potential through inhibiting the metastasis of gastric GIST.

KEYWORDS:

Gastrointestinal stromal tumors; Malignization; Metastasis; Microarray; SPARCL1

PMID:
29973149
PMCID:
PMC6030747
DOI:
10.1186/s12876-018-0833-8
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for BioMed Central Icon for PubMed Central
Loading ...
Support Center