OxLDL promotes lymphangiogenesis and lymphatic metastasis in gastric cancer by upregulating VEGF‑C expression and secretion

Ma,Caiqi; Xie,Jinye; Luo,Chuanghua; Yin,Haofan; Li,Ruopu; Wang,Xi; Xiong,Wenjun; Zhang,Ting; Jiang,Ping; Qi,Weiwei; Zhou,Ti; Yang,Zhonghan; Wang,Wei; Ma,Jianxing; Gao,Guoquan; Yang,Xia

doi:10.3892/ijo.2018.4648

OxLDL promotes lymphangiogenesis and lymphatic metastasis in gastric cancer by upregulating VEGF‑C expression and secretion

Authors:
- Caiqi Ma
- Jinye Xie
- Chuanghua Luo
- Haofan Yin
- Ruopu Li
- Xi Wang
- Wenjun Xiong
- Ting Zhang
- Ping Jiang
- Weiwei Qi
- Ti Zhou
- Zhonghan Yang
- Wei Wang
- Jianxing Ma
- Guoquan Gao
- Xia Yang
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Affiliations: Department of Internal Medicine, Affiliated Guangzhou Women and Children's Medical Center, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Biochemistry, Zhongshan School of Medicine, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Gastrointestinal Surgery, Traditional Chinese Medicine Hospital of Guangdong Province, Guangzhou, Guangdong 510080, P.R. China, Department of Laboratory Medicine, The Second Affiliated Hospital of South China University of Technology, Guangzhou, Guangdong 510080, P.R. China, Department of Physiology, University of Oklahoma, Health Sciences Center, Oklahoma City, OK 73104, USA
Published online on: November 26, 2018 https://doi.org/10.3892/ijo.2018.4648
Pages: 572-584
Copyright: © Ma et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Gastric cancer is one of the most malignant tumor types, and its metastasis is a notable cause of mortality. Among the methods of tumor metastasis, lymphatic metastasis is the predominant one in gastric cancer. A previous study reported that the plasma oxidized low‑density lipoprotein (oxLDL) is the risk factor associated with the development of tumors in patients with abnormal lipid metabolism, but the influence of plasma oxLDL in the lymphatic metastasis of gastric cancer remains unclear. In the present study, the concentration of plasma oxLDL from patients with gastric cancer was detected with an ELISA kit, and the lymphatic vessel density in gastric cancer tissues was determined by D2‑40 staining. The correlation analysis of oxLDL concentration and lymphatic vessel density demonstrated that plasma oxLDL was positively correlated with lymphatic metastasis in patients with gastric cancer. Subsequently, the popliteal lymph node metastasis animal experiment with nude mice confirmed that oxLDL could promote the lymphatic metastasis of gastric cancer. Following this, the western blotting and ELISA data demonstrated that oxLDL promoted the expression and secretion of vascular endothelia growth factor (VEGF)‑C in gastric cancer cell lines. Finally, blocking the lectin‑like oxLDL‑1 (LOX‑1) receptor, a specific receptor for oxLDL, and the nuclear factor (NF)‑κB signaling pathway following oxLDL (50 µg/ml) treatment in HGC‑27 cells revealed that oxLDL could activate the NF‑κB signaling pathway mediated by LOX‑1, with subsequent upregulation of VEGF‑C expression, and secretion in and from gastric cancer cells, and finally that it could promote the lymphatic metastasis of gastric cancer. These data indicate the association between the plasma oxLDL and the lymphatic metastasis of gastric cancer, and indicate that oxLDL elimination may be a potential therapeutic target for the prevention and intervention of early lymph node metastasis in gastric cancer.

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