Panse J, Hipp M L, Bauer G
Abteilung Virologie, Institut für Medizinische Mikrobiologie und Hygiene, Universität Freiburg, Germany.
Carcinogenesis. 1997 Feb;18(2):259-64. doi: 10.1093/carcin/18.2.259.
The ability of neighbouring normal cells to inhibit proliferation of transformed cells is regarded as the classical mode of intercellular control of potential tumour cells. This mechanism, however, only controls the pool size of transformed cells, but does not impair their survival. We have recently shown that cells transformed by biological agents are subject to a novel control system: transforming growth factor beta (TGF-beta) induces normal cells to release factors that mediate apoptosis specifically in transformed cells. Here we show that cells transformed by chemical carcinogens are also subject to this dominant control mechanism. The number of foci induced by methylcholanthrene, N-methyl-N'-nitro-N-nitrosoguanidine or quercetin was significantly reduced when the cultures were treated with TGF-beta. Established lines of chemically transformed cells proved to be sensitive to induction of apoptosis by neighbouring normal cells in the presence of TGF-beta. This finding demonstrates that sensitivity to induction of apoptosis is a general feature of transformed cells, irrespective of the transforming agent. It is particularly relevant for chemical carcinogenesis. As transformed cells were shown to trigger induction of their own apoptosis, the acquisition of resistance to this process may be a central regulatory step in carcinogenesis in vitro and possibly also in vivo. This study may help to elucidate mechanisms that protect transformed cells at an early stage of tumour progression that has until now not been the focus of investigation.
相邻正常细胞抑制转化细胞增殖的能力被视为对潜在肿瘤细胞进行细胞间控制的经典模式。然而，这种机制仅控制转化细胞的群体大小，而不会损害它们的存活。我们最近发现，由生物制剂转化的细胞受到一种新型控制系统的调控：转化生长因子β（TGF-β）诱导正常细胞释放特异性介导转化细胞凋亡的因子。在此我们表明，由化学致癌物转化的细胞也受这种主要控制机制的影响。当用TGF-β处理培养物时，甲基胆蒽、N-甲基-N'-硝基-N-亚硝基胍或槲皮素诱导的病灶数量显著减少。在TGF-β存在的情况下，已建立的化学转化细胞系被证明对相邻正常细胞诱导的凋亡敏感。这一发现表明，对凋亡诱导的敏感性是转化细胞的一个普遍特征，与转化剂无关。这对于化学致癌作用尤为重要。由于已证明转化细胞会触发自身凋亡的诱导，因此获得对这一过程的抗性可能是体外乃至体内致癌作用中的一个核心调控步骤。这项研究可能有助于阐明在肿瘤进展早期保护转化细胞的机制，而这一机制迄今为止尚未成为研究的重点。
