PREVENTION OF PERITONEAL METASTASIS -INHIBITION OF VASEMENT MEMBRANE DESTRUCTION

我们以前的研究表明，阻断肿瘤细胞与基底膜的附着和破坏基底膜可以抑制腹膜转移。1)肿瘤细胞内层粘连蛋白受体的免疫组织化学研究。多种肿瘤细胞表面均可检测到受体，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。层粘连蛋白受体的表达可能与肿瘤细胞周期有关。2)注射受体配体能抑制着床吗？注射层粘连蛋白的小鼠存活时间仅比对照组短。层粘连蛋白(LN)和丝裂霉素C(MMC)注射比单独注射丝裂霉素C的存活时间更长。扫描电子显微镜观察LN+MMC注射组移植瘤细胞较少。合成层粘连蛋白五肽(YIGSR)对此无影响。这些研究表明，层粘连蛋白受体配体的开发对于抗粘连治疗的临床应用是必不可少的。3)用免疫组织化学方法观察组织金属蛋白酶抑制物(TIMP)、基质金属蛋白酶(MMPs)的表达。肿瘤细胞周围可见基质金属蛋白酶过度增殖和侵袭。在肿瘤细胞种植期间，TIMP在浆膜下间隙内可见增强。在基底膜破坏和侵袭浆膜下间隙期间，TIMP在浆膜下间隙和周围侵袭的肿瘤细胞中进一步增强，提示TIMP具有抑制肿瘤转移的作用。

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.