Expression and prognostic significance of cadherin and detection system of ciculating cancer cells in renal cell carcinoma

肾细胞癌中钙粘蛋白的表达及预后意义及循环癌细胞检测系统

基本信息

批准号：
10671457
负责人：
SHIMAZUI Toru
金额：
$ 0.96万
依托单位：
University of Tsukuba
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2000
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10671457/
关键词：
Renal cell carcinoma Cadherin metastasis RT-PCR prognostic factor 腎細胞癌転移 Reual cell carcinoma cadherin cell adhesion molecule cateuin metastasis prognosis

项目摘要

Most renal cell carcinomas (RCCs) do not express E-cadheirn as well as renal proximal tubular epithelium. Instead of this, RCC frequently expresses cadheirn-6 and N-cadherin and cadherin-6 correlated with biological behavior of RCC cell line in vitro. Thus, we investegated whether cadherin-6 was a useful molecular marker in RCC using monoclonal antibody against human cadherin-6. Abnormal expression of cadherin-6 was observed in 24 of 43 RCC patients and those patients siginificantly had a poorer prognosis, specially in the patietns with E-cadherin-absent RCC.Since expression of cadherin-6 and N-cadherin was preserved in the metastatic site of RCC, we next studied that RCC cells could be detected in circulating blood using RT-PCR for these specific cadherin mRNA.Both of cadheirn-6 and N-cadherin were expressed in RCC cell line, normal kidney and RCC specimens. However, in the peripheral blood from healthy volunteers N-cadherin mRNA was frequently detected using nested RT-PCR system. Cadherin-6 mRNA was observed in 11 out of 15 patietns with metastasis, whereas in 6 out of 12 patients withour metastasis of RCC.It has been considered that quantitative nanalyses should be needed to stabilize the sensitivity of this PCR assay, so that we reanalysed the expression level of cadherin-6 mRNA in peripheral blood using quantitative RT-PCR.After cut off level of cadhiern-6 mRNA was determined in healthy volunteers, cadherin-6 mRNA was detected in 9 out of 13 patietns with metastatic RCC.In contrast, in 36 RCC patients withour metastasis, cadheirn-6 mRNA was detected in 13 patietns before nephrectomy and it decreased into normal range in 6 patients after surgery. Quantitative RT-PCR for Cadherin-6 might be a useful tool to detect RCC cells in ciculating blood in RCC patients.

大多数肾细胞癌 (RCC) 不表达 E-钙粘蛋白以及肾近端肾小管上皮。相反，RCC 经常表达与 RCC 细胞系体外生物学行为相关的 cadheirn-6 和 N-cadherin 和 cadherin-6。因此，我们使用抗人 cadherin-6 的单克隆抗体研究了 cadherin-6 是否是 RCC 中有用的分子标记。在 43 例 RCC 患者中，有 24 例观察到 cadherin-6 表达异常，这些患者的预后明显较差，特别是在 E-cadherin 缺失的 RCC 患者中。因为 cadherin-6 和 N-cadherin 的表达在转移性肾细胞癌中得以保留。针对 RCC 部位，我们接下来研究了可以使用 RT-PCR 检测循环血液中这些特定钙粘蛋白 mRNA 的 RCC 细胞。 cadheirn-6 和 N-cadherin 在 RCC 细胞系、正常肾脏和 RCC 标本中表达。然而，巢式 RT-PCR 系统经常在健康志愿者的外周血中检测到 N-钙粘蛋白 mRNA。 15 例有转移的肾细胞癌患者中，有 11 例检测到了 Cadherin-6 mRNA，而在 12 例没有转移的肾细胞癌患者中，有 6 例检测到了 Cadherin-6 mRNA。人们认为需要进行定量分析来稳定该 PCR 检测的灵敏度，因此我们重新分析了采用定量RT-PCR检测外周血中cadherin-6 mRNA的表达水平。测定健康志愿者中cadhiern-6 mRNA的截止水平后， 13例转移性肾细胞癌患者中，9例检测到cadherin-6 mRNA。相比之下，36例无转移的肾细胞癌患者，肾切除前13例检测到cadheirn-6 mRNA，术后6例下降至正常范围。 Cadherin-6 定量 RT-PCR 可能是检测 RCC 患者循环血液中 RCC 细胞的有用工具。