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The analysis of thymidine phospholyrase and mucin expression related to invasion and metastasis in pancreas cancer

胰腺癌中胸苷磷酸化酶和粘蛋白表达与侵袭转移相关性分析

基本信息

批准号：
14571212
负责人：
NATSUGOE Shoji
金额：
$ 2.18万
依托单位：
Kagoshima University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

We found the close relationship between overexpression of thymidine phosphorylase(TP) or membrane-bound type mucin(MUC1) and hematogeneous metastasis or poor prognosis in various type of cancer. The incidence of TP overexpression was high in pancreatic cancer. Cell movement and invasion was promoted by TP, but apoptosis was suppressed by TP. TP was closely related to invasion and metastasis in cancer cell because TP inhibitor suppressed the expression of TP. Furthermore, we found that TP was related to the HIF-1 pathway in avoidance of apoptosis. MUC1 expression correlated well with the malignant biological behavior in pancreatic cancer. We reported the new classification of intraductal papillary-mucinous tumor in the pancreas by intestinal type secretory mucin(MUC2) expression.Pancreatic cancer is one of the most aggressive cancers in solid tumor. The high incidence of recurrent disease was found after curative resection. We examined the presence of lymph node micrometastasis in pancreatic cancer. Lymph node micrometastasis was highly found even in pN0 pancreatic cancer. The clinical significance should be clarified in the large number of patients, especially in the distant lymph node micrometastasis.The expression of VEGF-C and -D was immunohistochemically examined in pancreatic cancer. The incidence of VEGF-C and -D overexpression was significantly higher in the marginal portion than in the central portion of the tumor. Prognosis of patients with high expression of both VEGF-C and -D in the marginal portion was significantly poorer than that of patients with loe expression of both VEGF-C and -D. The examination of VEGF-C and -D expression by biopsy specimens will be useful to predict the malignant property in pancreatic cancer.

我们发现胸苷磷酸化酶(TP)或膜结合型粘蛋白(MUC1)的过度表达与不同类型肿瘤的血行转移或预后不良密切相关。TP过表达在胰腺癌中的发生率较高。茶多酚促进细胞运动和侵袭，但抑制细胞凋亡。TP抑制剂抑制TP的表达，与肿瘤细胞的侵袭转移密切相关。此外，我们还发现TP与HIF-1途径有关，从而避免了细胞的凋亡。MUC1的表达与胰腺癌的恶性生物学行为密切相关。根据肠型分泌粘蛋白(MUC2)的表达对胰腺导管内乳头状黏液性肿瘤进行了新的分类。胰腺癌是实体瘤中侵袭性最强的肿瘤之一。根治性切除后复发率高。我们检查了胰腺癌中是否存在淋巴结微转移。即使在pN0胰腺癌中，也有较高的淋巴结微转移。对胰腺癌组织中的血管内皮生长因子C和血管内皮生长因子D的表达进行免疫组织化学检测。肿瘤边缘部位的VEGF-C和-D过度表达的发生率明显高于肿瘤中心部位。边缘区同时高表达VEGF-C和-D的患者预后明显差于同时表达LOE的患者。检测胰腺癌活检标本中VEGF-C和-D的表达有助于预测胰腺癌的恶性程度。