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Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors
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 explore...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030747/ https://www.ncbi.nlm.nih.gov/pubmed/29973149 http://dx.doi.org/10.1186/s12876-018-0833-8 |
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author | Shen, Chaoyong Yin, Yuan Chen, Huijiao Wang, Ruixue Yin, Xiaonan Cai, Zhaolun Zhang, Bo Chen, Zhixin Zhou, Zongguang |
author_facet | Shen, Chaoyong Yin, Yuan Chen, Huijiao Wang, Ruixue Yin, Xiaonan Cai, Zhaolun Zhang, Bo Chen, Zhixin Zhou, Zongguang |
author_sort | Shen, Chaoyong |
collection | PubMed |
description | 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-018-0833-8) contains supplementary material, which is available to authorized users. |
format | Online Article Text |
id | pubmed-6030747 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-60307472018-07-09 Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors Shen, Chaoyong Yin, Yuan Chen, Huijiao Wang, Ruixue Yin, Xiaonan Cai, Zhaolun Zhang, Bo Chen, Zhixin Zhou, Zongguang BMC Gastroenterol Research Article 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. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12876-018-0833-8) contains supplementary material, which is available to authorized users. BioMed Central 2018-07-04 /pmc/articles/PMC6030747/ /pubmed/29973149 http://dx.doi.org/10.1186/s12876-018-0833-8 Text en © The Author(s). 2018 Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. |
spellingShingle | Research Article Shen, Chaoyong Yin, Yuan Chen, Huijiao Wang, Ruixue Yin, Xiaonan Cai, Zhaolun Zhang, Bo Chen, Zhixin Zhou, Zongguang Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title | Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title_full | Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title_fullStr | Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title_full_unstemmed | Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title_short | Secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
title_sort | secreted protein acidic and rich in cysteine-like 1 suppresses metastasis in gastric stromal tumors |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030747/ https://www.ncbi.nlm.nih.gov/pubmed/29973149 http://dx.doi.org/10.1186/s12876-018-0833-8 |
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