Apoptosis and metastasis: Increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms
Apoptosis and metastasis: Increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms
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DOI：
10.1016/s0304-3835(97)04738-1
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发表时间：
1997-05-19
期刊：
影响因子：
9.7
通讯作者：
Hueser, CJ
中科院分区：
文献类型：
--
作者：
Glinsky, GV;Glinsky, VV;Hueser, CJ
程序性细胞死亡，特别是细胞存活和凋亡的粘附依赖性调节，被认为是控制细胞定位、消除错位细胞和阻止转移传播的主要稳态机制之一。最近我们报道，与低转移性癌细胞相比，高转移性癌细胞对程序性细胞死亡表现出更高的抵抗力。， 101, 43-51, 1996)。然而，侵袭性转移表型与抗凋亡相关的分子和遗传基础仍有待阐明。在这里，我们扩展了对细胞凋亡和转移的研究，使用了9种具有不同转移潜力的小鼠和人类癌细胞系。我们研究了转移能力与细胞凋亡敏感性之间的关系，并确定了两种主要的细胞凋亡执行机制（核Ca2+依赖性内切酶的诱导和ice样蛋白酶的激活）在具有不同转移潜力和不同细胞凋亡敏感性的癌细胞中的状态。我们发现，高转移潜能与细胞凋亡抗性增加、细胞核Ca2+依赖性内切酶水平降低和CPP32/Yama死亡蛋白酶活性显著降低密切相关。我们的结论是，转移性癌细胞对细胞凋亡的高抗性与主要细胞凋亡执行机制的严重缺陷有关，也可能取决于这种机制。(C) 1997爱思唯尔科学爱尔兰有限公司
Programmed cell death, particularly adhesion-dependent regulation of cell survival and apoptosis, is recognized as one of the main homeostatic mechanisms designed to control cell positioning, eliminate misplaced cells and block metastatic dissemination. Recently we reported that highly metastatic cancer cells exhibit a higher resistance to the programmed cell death compared to their poorly metastatic counterparts (Cancer Lett., 101, 43-51, 1996). However, the molecular and genetic basis for the association of aggressive metastatic phenotype with resistance toward apoptosis remains to he elucidated. Here we extended our investigation on apoptosis and metastasis using a panel of nine murine and human cancer cell lines with different metastatic potential. We examined the relationship of the metastatic ability and the sensitivity to apoptosis as well as determined the status of two major apoptosis execution mechanisms (induction of nuclear Ca2+-dependent endonucleases and activation of ICE-like proteases) in cancer cells with distinct metastatic potential and different sensitivity to apoptosis. We found that high metastatic potential is strictly associated with the increased resistance to apoptosis, diminished level of nuclear Ca2+-dependent endonucleases, and significantly reduced activity of CPP32/Yama death protease. We concluded that high resistance to apoptosis of metastatic cancer cells is associated with and may depend upon the profound deficiency of major apoptosis execution mechanisms. (C) 1997 Elsevier Science Ireland Ltd.