Apoptosis, tumour invasion and prostate cancer
Apoptosis, tumour invasion and prostate cancer
复制标题
DOI：
10.1111/j.1464-410x.1997.tb16918.x
复制
发表时间：
1997-04-01
期刊：
影响因子：
--
通讯作者：
Tenniswood, M
中科院分区：
文献类型：
--
作者：
Tenniswood, M
细胞死亡或凋亡不是一种单一的现象，而是一系列形态学和生物化学相关的过程[1，2]。淋巴细胞和其他网状内皮起源细胞的细胞死亡主要由核形态学变化[3]控制，而腺上皮细胞（如前列腺细胞）的凋亡性死亡需要细胞质的深刻变化以及细胞-细胞和细胞-基质相互作用的改变[4]。啮齿类动物前列腺是研究激素戒断诱导细胞凋亡的一个非常有用的模型。前列腺是一个树枝状的导管网络，具有几种细胞类型，显示出解剖学和生化异质性以及对雄激素消融的显著不同的敏感性。分泌性上皮细胞位于导管的远端和中间区域[S-71，并且严重依赖雄激素存活[8]。在导管的近端区域，管腔上皮细胞没有分泌活性[6，9]。无论是这些细胞，还是也位于近端区域的基底细胞，似乎都不需要雄激素来生存。前列腺在去势后约12小时开始消退，此时Sct-DHT福尔斯水平降至抑制退化所需的水平以下[lo]。在接下来的3-6天内发生的前列腺大小的减小主要是由于远端和中间区域中的分泌性管腔上皮细胞的选择性损失，导致许多导管完全闭塞，同时在去势后保持导管的近端段。前列腺细胞凋亡的过程可以分为几个阶段（图1）。在预浓缩阶段，许多细胞死亡所必需的基因被诱导死亡，或者从腺体的其他功能中招募。预缩合阶段的长度似乎因细胞而异，可能反映了激素或生长因子环境的微观异质性。预凝聚阶段之后是细胞质凝聚，其涉及死亡细胞与其相邻细胞之间的相互作用的丧失，因为细胞外基质（ECM）被降解并且细胞质体积减小。在核浓缩过程中，一种或多种核酸内切酶的激活导致DNA片段化及其边缘化到核周边，产生凋亡细胞特有的深染、固缩核。由于腺组织中细胞凋亡的启动是随机的，因此很难在体内时间上清楚地分离细胞质和核凝聚，但在来自其他组织的分离细胞（例如颗粒细胞）中，核凝聚在细胞质凝聚之后清楚地启动。在片段化阶段，凋亡细胞被细分为几个凋亡小体，其随后被邻近的上皮细胞或巨噬细胞吞噬，并被宿主细胞或凋亡小体中激活的溶酶体酶降解[111]。值得注意的是，后一个过程发生时，细胞内-Mar组分没有泄漏到细胞外空间，确保补体级联系统没有被激活，并且没有炎症反应。这一特征将凋亡与坏死区分开来。在前列腺中，细胞质和细胞核浓缩似乎需要3-5分钟，其余可见的凋亡阶段在3-4小时内完成，需要RNA和蛋白质合成[12，13]。
Cell death, or apoptosis, is not a single phenomenon but a series of morphologically and biochemically related processes [1, 2]. Cell death of lymphocytes and other cells of reticulo-endothelial origin is dominated by changes in nuclear morphology [3], while apoptotic death of glandular epithelial cells, such as those of the prostate, requires profound cytoplasmic changes and alterations in the cell-cell and cell-substratum interactions [4]. The rodent prostate is a very useful model for the study of apoptosis induced by hormone withdrawal, The gland is an arborhed network of ducts, with several cell types that display anatomical and biochemical heterogeneity and substantially different sensitivities to androgen ablation. The secretory epithelial cells are localized to the distal and intermediate regions of the ducts [S-71 and are critically dependent on androgens for survival [8]. In the proximal region of the ducts, the luminal epithelial cells have no secretory activity [6, 9]. Neither these cells, nor the basal cells that are also localized to the proximal region, appear to require androgens for survival. The prostate begins to regress about 12 h after castration, when the level of Sct-DHT falls below that needed to inhibit involution [lo]. The reduction in prostate size that occurs over the next 3-6 days is primarily due to the selective loss of the secretory luminal epithelial cells in the distal and intermediate regions, resulting in the complete obliteration of many of the ducts while maintaining the proximal segments of the ducts after castration. The process of apoptosis in the prostate can be broken down into several stages (Fig. 1). During the precondensation stage, many of the genes that are necessary for cell death are induced de now, or recruited from other functions in the gland. The length of the precondensation stage appears to vary from cell to cell and probably reflects the microheterogeneity in the hormone or growth factor environment. The precondensation phase is followed by cytoplasmic condensation which involves the loss of the interactions between the dying cell and its neighbours as the extra-cellular matrix (ECM) is degraded and the cytoplasmic volume decreases. During nuclear condensation, the activation of one or more endonucleases results in the fragmentation of the DNA and its marginalization to the nuclear periphery, Producing the hyperchromatic, pyknotic nucleus characteristic of apoptotic cells. As the initiation of apoptosis in glandular tissues is stochastic, it is difficult to separate clearly cytoplasmic and nuclear condensation temporally in vivo, but in isolated cells from other tissues (eg granulosal cells), nuclear condensation is clearly initiated after cytoplasmic condensation. During the fragmentation phase the apoptotic cell is subdivided into several apoptotic bodies which are subsequently phagocytosed by the neighbouring epithelial cells or macrophages and degraded by the lysosomal enzymes, activated either in the host cell or in the apoptotic body [l 11. Remarkably, this latter process occurs with no leakage of the intracel-Mar components into the extracellular space, ensuring that the complement cascade system is not activated and that there is no inflammatory response. This feature distinguishes apoptosis from necrosis. In the prostate, cytoplasmic and nuclear condensation appear to take 3-5 min and the remaining visible stages of apoptosis are completed within 3-4 h and require both RNA and protein synthesis [12, 13].