The new approach of radiotherapy for the prevention of metastasis

1. Bcl-2结合蛋白BAG-1被鉴定为抗凋亡分子，并与Raf-1、Hsp 7 O/Hsc 7 O、类固醇激素和肝细胞生长因子（HGF）受体结合，暗示BAG-1的多功能。为了探索放射抑制肿瘤转移的方法，我们建立了一种通过过表达BAG-1或Bcl-2调节胃癌细胞转移潜能的动物模型。也就是说，BAG-1在人胃癌细胞中的过表达导致抗失巢凋亡的细胞存活延长和腹膜播散增加。此外，我们证明BAG-1的过表达强烈增强了人胃癌细胞的运动性。在胃癌MKN 74细胞中，BAG-1过表达，BAG-1与细胞角蛋白共定位，并在溶血磷脂酸（LPA）诱导下集中在膜皱褶处，导致与肌动蛋白部分共定位。这些数据有力地表明BAG-1在上皮细胞功能中的协同作用。 ...更多信息 骨骼蛋白两个独立的迁移试验表明，与对照转染子或亲本MKN 74细胞相比，表达BAG-1的MKN 74细胞表现出其迁移的强烈增强。在MKN 74细胞中，BAG-1的过表达既不影响细胞的粘附能力，也不影响细胞对HGF的反应，在另一种人胃癌细胞系MKN 45中，BAG-1的转染子也观察到类似的促进细胞迁移的作用。综上所述，这些研究表明BAG-1是一个很好的候选靶分子，用于抑制胃癌转移.我们还研究了几个可能的因素，确定细胞凋亡的辐射敏感性。通过对20多个人肿瘤细胞株照射后JNK活性的研究，发现JNK活性的增加与肿瘤细胞对照射的敏感性密切相关.本研究观察了辐射对人腺癌细胞系原癌基因c-er B B-2和细胞间粘附分子-1（ICAM-1）表面抗原表达的影响。照射后细胞膜上ErB B-2蛋白和ICAM-1表达增加。结果提示，低剂量辐射可促进肿瘤局部LFA-1阳性细胞毒性T淋巴细胞（CTL）的聚集，从而使肿瘤细胞受到攻击。少

1. A Bcl-2-binding protein BAG-1 is identified as an anti-apoptotic molecule and binds to Raf-1, Hsp7O/Hsc7O, steroid hormone and hepatocyte growth factor (HGF) receptors, implicating multifunctions of BAG-1. In order to explore a method for suppression of cancer metastasis by irradiation, we establish an animal model which modulates metastasis potential of gastric cancer cells by overexpression of BAG-1 or Bcl-2. Namely, overexpression of BAG-1 in human gastric cancer cells led to prolonged cell survival against anoikis and increased peritoneal dissemination. In addition, we demonstrate that overexpression of BAG-1 strongly enhances the motility of human gastric cancer cells. In the gastric cancer MKN74 cells overexpression BAG-1, BAG1 colocalized with cytokeratin, and was concentrated at membrane ruffles induced by lysophosphatidic acid (LPA), resulting in partial colocalization with actin. These data strongly suggest cooperative roles of BAG-1 in the functions of epithelial cell cyt … More oskeletal proteins. Two independent migration assays showed that the BAG-1-expressing MKN74 cells exhibited strong enhancement of their migration compared with the control transfectants or parent MKN74 cells. In MKN74 cells, the overexpression of BAG-1 affected neither cell adhesion capability nor response to HGF.The promotive effect of BAG-1 on cell migration was similarly observed in transfectants of another human gastric cancer MKN45 cell line. Taken together, these studies demonstrate that BAG-1 is a good candidate as a target molecule for suppression of gastric cancer metastasis.2. We have also investigated several possible factors for determining apoptosis sensitivity to irradiation. By investigating JNK activity in more than 20 human cancer cell lines after irradiation, we found a tight correlation between an increase of JNK activity and sensitivity to irradiation-induced apoptosis.3. We have investigated the effect of irradiation on the surface antigen expression of proto-oncogene c-erb B-2 and intercellular adhesion molecule-1 (ICAM-l) on human adenocarcinoma cell lines. The expression ofthe Erb B-2 protein and ICAM-l on the cell membrane was found to increase by irradiation. The results suggest that the low dose radiation may be useful for accumulating LFA-1 positive cytotoxic T lymphocytes (CTL) at the local tumor tissue, which tumor cells may be attacked. Less