Biophysical and epigenetic regulation of cancer stemness, invasiveness and immune action.

Current tissue microenvironment reports Pub Date : 2020-12-01 Epub Date: 2020-11-02 DOI:10.1007/s43152-020-00021-w
Praveen Krishna Veerasubramanian, Annie Trinh, Navied Akhtar, Wendy F Liu, Timothy L Downing
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Abstract

Purpose of review: The tumor microenvironment (TME) is an amalgam of multiple dysregulated biophysical cues that can alter cellular behavior through mechanotransductive signaling and epigenetic modifications. Through this review, we seek to characterize the extent of biophysical and epigenetic regulation of cancer stemness and tumor-associated immune cells in order to identify ideal targets for cancer therapy.

Recent findings: Recent studies have identified cancer stemness and immune action as significant contributors to neoplastic disease, due to their susceptibility to microenvironmental influences. Matrix stiffening, altered vasculature, and resultant hypoxia within the TME can influence cancer stem cell (CSC) and immune cell behavior, as well as alter the epigenetic landscapes involved in cancer development.

Summary: This review highlights the importance of aberrant biophysical cues in driving cancer progression through altered behavior of CSCs and immune cells, which in turn sustains further biophysical dysregulation. We examine current and potential therapeutic approaches that break this self-sustaining cycle of disease progression by targeting the presented biophysical and epigenetic signatures of cancer. We also summarize strategies including the normalization of the TME, targeted drug delivery, and inhibition of cancer-enabling epigenetic players.

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癌症干性、侵袭性和免疫作用的生物物理和表观遗传调控。
综述的目的:肿瘤微环境(TME)是多种失调生物物理线索的混合体,可通过机械传导信号和表观遗传修饰改变细胞行为。通过这篇综述,我们试图描述癌症干性和肿瘤相关免疫细胞的生物物理和表观遗传调控程度,以确定癌症治疗的理想靶点:最近的研究发现,癌症干细胞和免疫作用是导致肿瘤疾病的重要因素,因为它们容易受到微环境的影响。摘要:本综述强调了异常生物物理线索在通过改变癌干细胞和免疫细胞的行为推动癌症进展方面的重要性,这反过来又维持了进一步的生物物理失调。我们研究了当前和潜在的治疗方法,这些方法通过针对癌症的生物物理和表观遗传特征来打破这种自我维持的疾病进展循环。我们还总结了包括TME正常化、靶向给药和抑制致癌表观遗传因子的策略。
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