权益分类	功能权益	普通用户	{{item.name}}会员
{{category.name}}	{{benefitItem.name}}

Identification of molecules responsible for invasion-independent pathway of blood-borne metastasis.

鉴定负责血源性转移的侵袭独立途径的分子。

基本信息

批准号：
14570126
负责人：
SUGINO Takashi
金额：
$ 2.24万
依托单位：
Fukushima Medical Univerisity
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 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-14570126/
关键词：
Cancer metastasis Invasion Metastasis-related gene Transfection SLPI Renal cell carcinoma Hepatocellular carcinoma Follicular thyroid carcinoma metastasis invasion angiogenesis Secretory leukocyte protease inhibitor 肝細胞癌腎細胞癌血

项目摘要

Establishment of mouse metastatic model and identification of metastasisl-related genes : We separated sublines and clonal cell lines different in metastatic potential ; 66C8 (a non-metastatic clone), 66HM and Lu10 (highly metastatic sublines to general organs), etc from a mouse mammary tumor cell line (MCH66P) metastasizing via an invasion-independent pathway. A comparative study using these cells demonstrated that invasion-independent metastasis is related to high angiogenesis activity, especially sinusoidal development of tumor vasculature. To identify candidate genes responsible for this type of metastasis we performed differential screening using suppressive subtractive hybridization (SSH) method. Pleiotrophin, Secretory leukocyte protease inhibitor (SLPD), S3B, etc. were cloned as differentially expressed genes in higher metastatic cells among the sublines and clonal cell lines. We next transfected the candidate genes in 66C8 cells. Of five genes SLPI promoted spontaneous metastatic potential to the lung and induced sinusoidal development of tumor vessels as an index of invasion-independent metastasis.Application of the invasion-independent metastasis model to human cancers : Histological examination using archival specimens of 10 common types of human cancers demonstrated that an invasion-independent metastatic pathway is possible in a wide variety of human cancers, especially in most cases of renal cell carcinomas, hepatocellular carcinomas and follicular thyroid carcinomas. Immunohistochemical study showed that SLPI, which promoted invasion-independent metastasis in the mouse model, was also highly expressed in real cell carcinoma.Further studies based on these results may enable us to identify novel genes related to cancer metastasis and may present new therapeutic strategies for the amelioration of human cancers.

小鼠乳腺癌转移模型的建立及转移相关基因的鉴定：从非侵袭性转移的小鼠乳腺癌细胞系（MCH 66 P）中分离出66 C8（非转移性克隆）、66 HM和Lu10（一般器官高转移性亚系）等具有不同转移潜能的亚系和克隆细胞系。使用这些细胞的比较研究表明，侵袭非依赖性转移与高血管生成活性有关，特别是肿瘤血管系统的正弦发育。为了确定候选基因负责这种类型的转移，我们进行了差异筛选使用抑制性消减杂交（SSH）方法。克隆了多效生长因子、分泌型白细胞蛋白酶抑制剂（SLPD）、S3B等在高转移细胞亚系和克隆细胞系中的差异表达基因。我们接下来将候选基因转染到66C8细胞中。在5个基因中，SLPI促进了自发转移到肺的可能性，并诱导肿瘤血管的窦状发展作为非侵袭性转移的指标。使用10种常见类型的人类癌症的存档标本进行的组织学检查表明，在各种各样的人类癌症中，特别是在大多数肾细胞癌、肝细胞癌和滤泡性甲状腺癌的情况下。免疫组化研究表明，SLPI在小鼠肿瘤模型中能促进非侵袭性转移，但在真实的细胞癌中也有高表达，基于此结果的进一步研究将有助于发现与肿瘤转移相关的新基因，并为人类肿瘤的治疗提供新的策略。