Abstract 5139: Thymidine phosphorylase expression correlate with lymphangiogenesis and angiogenesis in metastatic gastric cancer

Thymidine Phosphorylase (TP) (platelet-derived endothelial cell growth factor, PD-ECGF) is known as a proangiogenic factor. High TP expression in the primary tumor has been thought as a risk factor for hepatic and lymph node metastasis in patients with gastric adenocarcinoma. However, the molecular basis for induction of invasion and lymph node metastasis by TP and its therapeutic implication is largely unknown. First, as a pilot study, the (lymph)angiogenic activity (D2-40, LYVE-1, VEGFC, VEGFR3) and TP expressions were evaluated in resected tumor samples. Sixty patients of gastric cancer with metastatic lymph nodes and in 46 patients without lymph node metastasis were included. With immunohistochemical study, we demonstrated that tumoral and stromal TP expressions were moderately correlated (Pearson correlation = 0.455). TP expression was also correlated with depth of invasion and nodal stage. TP-positive tumors had also increased lymphovascular invasion compared with TP-negative tumors (P = 0.044), and node positive tumor had higher density of lymphatic vessels, and it is correlated with TP expression (P = 0.023). Then, we have shown that nude mice injected intraperitoneally with TP-overexpressing MKN-45 cells (MKN-45/TP) had decreased survival times compared with those injected with control cells (MKN-45/CV). MKN-45/TP tumors were more angiogenic (positive for CD31) and lymphangiogenic (positive for D2-40 and LYVE-1), and they were more invasive than MKN-45/CV tumors. A specific TP inhibitor, TPI, partially extended the survival period of TP tumor bearing mice, and its angiogenic activity was significantly reduced. All these findings imply that TP expression may be related to lymphangiogenesis in gastric cancer, and it could be further investigated as therapeutic targets for anti-metastatic therapy. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 5139. doi:10.1158/1538-7445.AM2011-5139