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血管邻近性决定肿瘤内代谢分带及由此产生的表型多样性

时间:2019-08-01 08:07 来源:www.haosftl.com 作者:好私服

以色列希伯来大学Eli Keshet团队在研究中取得进展。他们的最新研究揭示了血管邻近性决定的肿瘤内的代谢分带和由此导致的表型多样性。相关论文发表在2019年7月出版的《细胞—代谢》杂志上。

该研究组利用一种方法,能够根据肿瘤细胞与血管(BVs)的相对距离对功能齐全、无基质的肿瘤细胞进行追溯分类,从而揭示受到血管邻近性影响的全基因图谱、代谢图谱和生物学特性图谱。在移植的小鼠肿瘤和天然人胶质母细胞瘤(GBM)中,mTOR的活性都局限于离灌注血管最近的几层细胞。在这一血管周围层内的癌细胞以旺盛的合成代谢为特征,并通过运用大量的氧化磷酸化来违背Warburg原理。血管周围癌细胞获得的功能特征包括:增强的致瘤性、优越的迁移或侵袭能力,以及意料之外的特殊的化疗和放射耐药性,这些都依赖于mTOR。综上所述,该研究揭示了一个以前未被认识的现象:分级代谢分带直接影响多种侵袭性肿瘤特征的获得。

据了解,肿瘤细胞分别暴露于血源性因子或血管分泌因子时,会形成不同的代谢微环境,有利于非遗传性肿瘤细胞的多样化。


Title: Intra-Tumoral Metabolic Zonation and Resultant Phenotypic Diversification Are Dictated by Blood Vessel Proximity

Author: Saran Kumar, Husni Sharife, Tirzah Kreisel, Maxim Mogilevsky, Libat Bar-Lev, Myriam Grunewald, Elina Aizenshtein, Rotem Karni, Iddo Paldor, Tomer Shlomi, Eli Keshet

Issue&Volume:Volume30 Issue1

Abstract: Differential exposure of tumor cells to blood-borne and angiocrine factors results in diverse metabolic microenvironments conducive for non-genetic tumor cell diversification. Here, we harnessed a methodology for retrospective sorting of fully functional, stroma-free cancer cells solely on the basis of their relative distance from blood vessels (BVs) to unveil the whole spectrum of genes, metabolites, and biological traits impacted by BV proximity. In both grafted mouse tumors and natural human glioblastoma (GBM), mTOR activity was confined to few cell layers from the nearest perfused vessel. Cancer cells within this perivascular tier are distinguished by intense anabolic metabolism and defy the Warburg principle through exercising extensive oxidative phosphorylation. Functional traits acquired by perivascular cancer cells, namely, enhanced tumorigenicity, superior migratory or invasive capabilities, and, unexpectedly, exceptional chemo- and radioresistance, are all mTOR dependent. Taken together, the study revealed a previously unappreciated graded metabolic zonation directly impacting the acquisition of multiple aggressive tumor traits.

DOI: https://doi.org/10.1016/j.cmet.2019.04.003

Source: https://www.cell.com/cell-metabolism/fulltext/S1550-4131(19)30187-1

期刊信息

Cell Metabolism:《细胞—代谢》,创刊于2005年。隶属于细胞出版社,最新IF:22.415
官方网址:https://www.cell.com/cell-metabolism/home
投稿链接:https://www.editorialmanager.com/cell-metabolism/default.aspx


本期文章:《细胞—代谢》:Volume 30 Issue 1

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