Summary: As an angiogenic factor, thymidine phosphorylase (TP) expression in primary tumours has been thought to be a risk factor for lymph node (LN) and hepatic metastasis 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.
1Department of Pathology, Yanbian University Hospital, Yanji City, Jilin Province, China
2Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul, South Korea
3Department of Dermatology, Yanbian University Hospital, Yanji City, Jilin Province, China
4Cancer Metastasis Research Center, Yonsei University College of Medicine, Seoul
5Division of Medical Oncology, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul
6Department of Surgery, Yonsei University College of Medicine, Seoul
7Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, South Korea
Address for correspondence: Professor H-C. Jeung, Division of Medical Oncology, Department of Internal Medicine, Gangnam Severance Hospital, Cancer Metastasis Research Center, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, 120-752, Korea. E-mail: firstname.lastname@example.org
Received 18 July, 2013
Revised 28 November, 2013
Accepted 2 December, 2013