Jintuan Huang1,2,3, Yi Sun1,4,5, Hao Chen1,2,3, Yi Liao1,2,3, Senmao Li1,2,3, Chunyu Chen1,2,3, Zuli Yang6,7,8. 1. Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People's Republic of China. 2. Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China. 3. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, People's Republic of China. 4. Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China. 5. Breast Tumor Center, Sun Yat-Sen Memorial Hospital, Sun Yat-Sen University, Guangzhou, People's Republic of China. 6. Department of Gastrointestinal Surgery, The Sixth Affiliated Hospital of Sun Yat-Sen University (Guangdong Gastrointestinal and Anal Hospital), Sun Yat-Sen University, 26 Yuancun Erheng Road, Guangzhou, 510655, People's Republic of China. yzlhlj7068@163.com. 7. Guangdong Institute of Gastroenterology, Guangzhou, People's Republic of China. yzlhlj7068@163.com. 8. Guangdong Provincial Key Laboratory of Colorectal and Pelvic Floor Disease, Guangzhou, People's Republic of China. yzlhlj7068@163.com.
Abstract
BACKGROUND: ADAMTS5 has been reported to be involved in the progression of several human tumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC) remains poorly defined. METHODS: ADAMTS5 expression levels were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell lines and tissues, and the correlations between ADAMTS5 expression and clinicopathological features and survival were also examined. In vitro assays, including transwell assays, wound healing assays and cell adhesion assays, were employed to further explore the biological functions of ADAMTS5. A MAP kinase pathway microarray was used to identify the underlying mechanisms. The expression of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using IHC to determine correlations with angiogenesis in GC. RESULTS: ADAMTS5 expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5 was associated with gender, histological type, degree of differentiation, M stage, TNM stage and vascular invasion, and was also an independent indicator of a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited GC cell migration and invasion and enhanced cell adhesion to the extracellular matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects. Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1 expression and MVD. CONCLUSION: ADAMTS5 is downregulated in GC and suppresses tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and potentially acts as a novel prognostic marker and a potential therapeutic target in human GC.
BACKGROUND:ADAMTS5 has been reported to be involved in the progression of several humantumors. Nevertheless, the role of ADAMTS5 in gastric cancer (GC) remains poorly defined. METHODS:ADAMTS5 expression levels were analyzed by quantitative real-time PCR (qRT-PCR) and immunohistochemistry (IHC) in GC cell lines and tissues, and the correlations between ADAMTS5 expression and clinicopathological features and survival were also examined. In vitro assays, including transwell assays, wound healing assays and cell adhesion assays, were employed to further explore the biological functions of ADAMTS5. A MAP kinase pathway microarray was used to identify the underlying mechanisms. The expression of ADAMTS5 and ETS1 and the microvessel density (MVD) were also analyzed using IHC to determine correlations with angiogenesis in GC. RESULTS:ADAMTS5 expression was downregulated in gastric cancer tissues. Low expression of ADAMTS5 was associated with gender, histological type, degree of differentiation, M stage, TNM stage and vascular invasion, and was also an independent indicator of a poor prognosis for patients with GC. ADAMTS5 overexpression markedly inhibited GC cell migration and invasion and enhanced cell adhesion to the extracellular matrix (ECM), whereas knockdown of ADAMTS5 exerted the opposite effects. Furthermore, the ADAMTS5 expression status was negatively correlated with ETS1 expression and MVD. CONCLUSION:ADAMTS5 is downregulated in GC and suppresses tumor metastasis and angiogenesis by inhibiting ETS1-mediated changes in MVD and potentially acts as a novel prognostic marker and a potential therapeutic target in human GC.
Entities:
Keywords:
ADAMTS5; Angiogenesis; ETS1; Gastric cancer; MVD; Migration and invasion
Authors: Silvia Redondo-García; Carlos Peris-Torres; Rita Caracuel-Peramos; Juan Carlos Rodríguez-Manzaneque Journal: Matrix Biol Plus Date: 2020-12-30