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PREVENTION OF PERITONEAL METASTASIS -INHIBITION OF VASEMENT MEMBRANE DESTRUCTION

预防腹膜转移-抑制血管膜破坏

基本信息

批准号：
03670617
负责人：
YAMAMOTO Akira
金额：
$ 0.9万
依托单位：
SHIGA UNIVERSITY OF MEDICAL SCIENCE
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (C)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1993
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670617/
关键词：
peritoneal metastasis destruction of basement membrane prevention of B.M.laminin receptor receptor ligand antiadhesion therapy YIGSR TIMP & MMP Pelitoneal metastasis cleseruction of B.M.Prevention of B.M.anti-adresion therapy TI

项目摘要

Our previous study have sugested that the blocking of fumor cell attachment to thebasement membrane and destruction of basement membrane inhibits the peritoneal metastasis. 1) Immunohistochemical study of the laminin receptor in tumor cell. Recepor was detected on the surface of many tumor cells, but the immunoreactivity was not distributed uniformly. No immuno-reactivity was detected on several cells. It seems that laminin receptor expression is related to rumor cell cycle. 2) Can implantation be inhibited by injection of receptor ligand ? Injection of laminin only showed a shorter survival time than the control. Administration of laminin(LN) and mitomycin C(MMC)resulted in longer survival times than mitomycin C injection alone. Fewer inplanted tumor cell were obserbed by Scanning Electron Microscopy on LN with MMC injection group. YIGSR(syntetic laminin pentapeptide)had no effect. These study suggests that development of laminin receptor ligand is essential for clinical use of anti-adhesion therapy. 3)TIMP(Tissue Inhibitor of Metalloproteinase), MMP(Matrix Metallo-Proteinase) were observed immunohistochemically. MMP was observed the surrounding prolirerated and invaded tumor cells. Augmented TIMP was observed in subserosal space at period of tumor cell implantation. And at period of basement memprane-destruction and invading to subserosal space, TIMP augmented further in subserosal space and surrounding invaded tumor cells.These results suggested that TIMP is useful for inhibition of tumor metastasis.

我们的前期研究表明，阻断肿瘤细胞与基底膜的粘附，破坏基底膜，抑制肿瘤的腹膜转移。1)肿瘤细胞层粘连蛋白受体的免疫组化研究。许多肿瘤细胞表面可检测到受体，但免疫反应性分布不均匀。在几个细胞上未检测到免疫反应性。提示层粘连蛋白受体的表达与肿瘤细胞周期有关。2)注射受体配体能抑制着床吗？注射层粘连蛋白仅显示出比对照组更短的存活时间。层粘连蛋白（LN）和丝裂霉素C（MMC）的管理导致较长的生存时间比单独注射丝裂霉素C。扫描电镜观察发现，MMC注射组LN上种植的肿瘤细胞较少。YIGSR（syntetic laminin pentapeptide）则无作用。这些研究表明，开发层粘连蛋白受体配体对于临床应用抗粘连治疗是必要的。3）组织金属蛋白酶抑制剂（TIMP）、基质金属蛋白酶（MMP）的免疫组化观察。MMP在肿瘤细胞周围增殖、浸润。TIMP在肿瘤细胞种植期的浆膜下间隙表达增强。在基底膜破坏并向浆膜下浸润时，TIMP在浆膜下及周围浸润的肿瘤细胞中进一步增强，提示TIMP有抑制肿瘤转移的作用。