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

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.

• 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
• Journal: International journal of oncology (Int J Oncol) Vol. 54 Issue 2 Pg. 572-584 (02 2019) ISSN: 1791-2423 [Electronic] Greece
• PMID: 30483757 (Publication Type: Journal Article)

Chemical References

• Lipoproteins, LDL
• NF-kappa B
• OLR1 protein, human
• Scavenger Receptors, Class E
• VEGFC protein, human
• Vascular Endothelial Growth Factor C
• oxidized low density lipoprotein

Topics

• Aged
• Animals
• Cell Line, Tumor
• Female
• Gene Expression Regulation, Neoplastic
• Humans
• Lipoproteins, LDL (blood, genetics)
• Lymphangiogenesis (genetics)
• Lymphatic Metastasis
• Male
• Mice
• Middle Aged
• NF-kappa B (genetics)
• Risk Factors
• Scavenger Receptors, Class E (genetics)
• Signal Transduction (genetics)
• Stomach Neoplasms (blood, genetics, metabolism, pathology)
• Transcriptional Activation (genetics)
• Vascular Endothelial Growth Factor C (blood, genetics)
• Xenograft Model Antitumor Assays