PREVENTION OF PERITONEAL METASTASIS -INHIBITION OF VASEMENT MEMBRANE DESTRUCTION

我们之前的研究表明，阻断肿瘤细胞附着基底膜和破坏基底膜可抑制腹膜转移。1)肿瘤细胞层粘连蛋白受体的免疫组化研究。在许多肿瘤细胞表面检测到受体，但免疫反应性分布不均匀。一些细胞未检测到免疫反应性。层粘连蛋白受体的表达与细胞周期有关。2)注射受体配体能否抑制着床？注射层粘连蛋白的存活时间比对照组短。层粘连蛋白（LN）和丝裂霉素C（MMC）联合使用比单独注射丝裂霉素C更能延长存活时间。MMC注射组LN的扫描电镜观察到植入的肿瘤细胞较少。合成层粘连蛋白五肽（YIGSR）无明显影响。这些研究提示层粘连蛋白受体配体的发育对抗粘连治疗的临床应用至关重要。3)免疫组化观察组织金属蛋白酶抑制剂（TIMP）、基质金属蛋白酶（MMP）水平。MMP观察周围肿瘤细胞增生和浸润。肿瘤细胞着床期浆膜下间隙TIMP增强。在基底膜破坏期及向浆膜下腔浸润时，TIMP在浆膜下腔及浸润肿瘤细胞周围进一步增强。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.