a Moffitt Cancer Center and Research Institute , Tampa , FL , USA.
Cell Cycle. 2017 Oct 2;16(19):1739-1743. doi: 10.1080/15384101.2016.1231284. Epub 2016 Sep 16.
The inter- and intra-tumoral metabolic phenotypes of tumors are heterogeneous, and this is related to microenvironments that select for increased glycolysis. Increased glycolysis leads to decreased pH, and these local microenvironment effects lead to further selection. Hence, heterogeneity of phenotypes is an indirect consequence of altering microenvironments during carcinogenesis. In early stages of growth, tumors are stratified, with the most aggressive cells developing within the acidic interior of the tumor. However, these cells eventually find themselves at the tumor edge, where they invade into the normal tissue via acid-mediated invasion. We believe acid adaptation during the evolution of cancer cells in their niche is a Rubicon that, once crossed, allows cells to invade into and outcompete normal stromal tissue. In this study, we illustrate some acid-induced phenotypic changes due to acidosis resulting in more aggressiveness and invasiveness of cancer cells.
肿瘤的细胞内外代谢表型具有异质性,这与选择增强糖酵解的微环境有关。糖酵解增加会导致 pH 值降低,而这些局部微环境效应会导致进一步的选择。因此,表型的异质性是癌变过程中改变微环境的间接后果。在生长的早期阶段,肿瘤是分层的,最具侵袭性的细胞在肿瘤内部的酸性环境中发育。然而,这些细胞最终会发现自己处于肿瘤边缘,通过酸介导的侵袭进入正常组织。我们认为,癌细胞在其龛位中进化过程中的酸适应是一个卢比孔河,一旦跨越,就允许细胞侵入并与正常基质组织竞争。在这项研究中,我们说明了一些由于酸中毒导致的癌症细胞的酸性诱导表型变化,这些变化导致了癌症细胞的侵袭性和侵略性增加。
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