As an angiogenic factor, thymidine phosphorylase (TP) expression in primary tumours has been thought to be a risk factor for lymph node (LN) and hepaticmetastasis in patients with gastric adenocarcinoma. However, the molecular basis for the induction of metastasis by TP is largely unknown. We aim to elucidate the role of TP expression in gastric cancer neovascularisation and LN metastasis. The angiogenic and lymphangiogenic activity (CD31, D2-40, Ki-67, VEGFC, VEGFR3) and expression status of TP were detected in 103 resected human gastric carcinoma samples by immunohistochemistry. The influence of TP expression on neovascularisation and cancer cell invasion was further comparatively investigated in two groups of nude mice intraperitoneally injected with TP overexpressing MKN-45 cells (MKN-45/TP) and control cells (MKN-45/CV). In gastric cancer tissues, we found that high TP expression and various angiogenic and lymphangiogenic activities were significantly associated with poor prognostic outcomes. In addition, TP expression was also found to be associated with neovascularisation activity of gastric cancer tissues. In vivo, the MKN-45/TP group exhibited significantly increased infiltrating tumour nodules and neovascularisation activity compared to the MKN-45/CV group. TP could strongly influence gastric cancer progression via the dual activities of angiogenesis and lymphangiogenesis.
Bibliographical noteFunding Information:
Jeung’s research was supported by the Korea Research Foundation Grant funded by the Korean Government (MOEHRD, Basic Research Promotion Fund) (KRF-2008–331-E00134). This work was also partly supported by a faculty research grant of Yonsei University College of Medicine (6–2008–0098) and Priority Research Centers Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2009–0094027).
All Science Journal Classification (ASJC) codes
- Pathology and Forensic Medicine