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.
Pathology. 2014 Jun;46(4):316-24. doi: 10.1097/PAT.0000000000000094.
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.
作为一种血管生成因子，胸苷磷酸化酶（TP）在原发性肿瘤中的表达被认为是胃腺癌患者淋巴结（LN）和肝转移的危险因素。然而，TP 诱导转移的分子基础在很大程度上尚不清楚。我们旨在阐明 TP 表达在胃癌血管生成和 LN 转移中的作用。通过免疫组织化学检测了 103 例人胃癌切除标本中的血管生成和淋巴管生成活性（CD31、D2-40、Ki-67、VEGFC、VEGFR3）和 TP 表达状态。通过向两组裸鼠腹腔内注射过表达 TP 的 MKN-45 细胞（MKN-45/TP）和对照细胞（MKN-45/CV），进一步比较研究了 TP 表达对血管生成和癌细胞侵袭的影响。在胃癌组织中，我们发现高 TP 表达和各种血管生成和淋巴管生成活性与不良预后结果显著相关。此外，TP 表达还与胃癌组织的血管生成活性有关。在体内，与 MKN-45/CV 组相比，MKN-45/TP 组表现出明显增多的浸润性肿瘤结节和血管生成活性。TP 可以通过血管生成和淋巴管生成的双重作用强烈影响胃癌的进展。
