Kallistatin inhibits lymphangiogenesis and lymphatic metastasis of gastric cancer by downregulating VEGF-C expression and secretion

Abstract

These findings demonstrated that kallistatin functions as an endogenous lymphangiogenesis inhibitor and has an important part in the lymphatic metastasis of gastric cancer.

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

“…4D and E). As our previous study verified, IKK-dependent phosphorylation of IκB and P65 was responsible for the positive transcriptional regulation of VEGF-C, and demonstrated that P65 was directly involved in the transcription of VEGF-C on the promoter region of VEGF-C using a chromatin immunoprecipitation assay (24). Thus, it is necessary to clarify whether oxLDL mediates the upregulation of VEGF-C by P65.…”

“…The previous data confirmed the role of oxLDL in promoting the lymph node metastasis of gastric cancer, but the molecular mechanism remains unclear. On the basis of previous studies, including our own (24,25), VEGF-C is a verified major VEGF that promotes lymphangiogenesis and lymph node metastasis. To investigate the mechanism of oxLDL in promoting lymph node metastasis, the effect of oxLDL on VEGF-C expression in and secretion from gastric cancer cells was examined, and the association between the concentration of plasma oxLDL and VEGF-C in patients with gastric cancer was analyzed.…”

“…Previous studies, including our own, have revealed that NF-κB signaling can regulate the expression of VEGF-C (24,26), and that oxLDL can promote the activation of the NF-κB signaling pathway (27,28). Therefore, the present study investigated whether oxLDL regulates the expression and secretion of VEGF-C through the NF-κB signaling pathway in gastric cancer cells.…”

“…There is sufficient evidence (34,35), including our previous data (24), to verify that lymphangiogenesis is a primary step for lymphatic metastasis and an important indicator for the aggressiveness of malignancies. Furthermore, studies also demonstrated that various malignancies, including breast, ovarian and cervical cancer, could induce the abnormal growth of peripheral lymphatic vessels and increase their permeability by secreting VEGF-C in order to facilitate the lymphatic metastasis of tumor cells (36,37).…”

“…To confirm that the enlargement of popliteal lymph nodes in nude mice was due to metastasized gastric cancer cells rather than tumor-induced inflammation, the metastasized gastric cancer cells were traced via live imaging with IVIS system. Prior to footpad injection, the HGC-27 cells were labeled with luciferase and then observed with the IVIS system as described previously (24). Finally, the results demonstrated that there were increased popliteal lymph node metastatic cancer cells migrating from footpad xenografts in the nLDL and oxLDL groups, compared with the control group, whilst oxLDL promoted lymphatic metastasis, primarily from orthotopic implantation (Fig.…”