Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and their association with tumor angiogenesis

Lu,Yanjie; Xu,Qian; Chen,Lei; Zuo,Yanzhen; Liu,Shaochen; Hu,Yatao; Li,Xiaoru; Li,Yuhong; Zhao,Xiangyang

doi:10.3892/ol.2016.5208

Expression of semaphorin 6D and its receptor plexin-A1 in gastric cancer and their association with tumor angiogenesis

Authors:
- Yanjie Lu
- Qian Xu
- Lei Chen
- Yanzhen Zuo
- Shaochen Liu
- Yatao Hu
- Xiaoru Li
- Yuhong Li
- Xiangyang Zhao
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Affiliations: Department of Pathology, Chengde Medical College, Chengde, Hebei 067000, P.R. China, Cancer Research Laboratory, Chengde Medical College, Chengde, Hebei 067000, P.R. China, Department of General Surgery, The 266th Hospital of Chinese People's Liberation Army, Chengde, Hebei 067000, P.R. China, Department of Gynecology and Obstetrics, The Central Hospital of Chengde City, Chengde, Hebei 067000, P.R. China
Published online on: September 29, 2016 https://doi.org/10.3892/ol.2016.5208
Pages: 3967-3974

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Abstract

The semaphorin and plexin family of ligands and receptor proteins provides important axon growth and guidance cues required for development. In recent years, studies have expanded their role in the regulation of cardiac morphogenesis and tumorigenesis. However, the mechanism responsible for their role in regulating cancer development and progression has not been clarified. In the present study, semaphorin 6D (Sema6D) and its receptor plexin‑A1 were identified to be expressed at high levels in vascular epithelial cells within gastric cancer, and were positively correlated with vascular endothelial growth factor receptor 2 (VEGFR2). These findings verify our hypothesis that Sema6D and plexin‑A1 may be closely associated with tumor angiogenesis. Combined with experimental observations in the MGC803 gastric cancer cell line, it was observed that knocking down plexin‑A1 signaling led to a decreased expression of VEGFR2 at the messenger RNA and protein levels. Sema6D recognized and activated plexin‑A1, which subsequently activated its downstream target, VEGFR2. The activation of VEGFR2 functioned as a positive regulator of tumor angiogenesis. Our data provided an understanding of the complex signaling cascades involved in the angiogenesis‑related pathway in tumor cells. In light of our observations, pharmacological interventions targeting Sema6D/plexin‑A1/VEGFR2 signaling may potentially be used as a target for the development of novel anti-angiogenic drugs in gastric cancer.

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