肿瘤组织力学异质性与肿瘤细胞的上皮-间质转化
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1.重庆大学生物工程学院;2.生物流变科学与技术教育部重点实验室,重庆大学生物工程学院

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Q 66

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Mechanical heterogeneity of tumor tissue and epithelial-mesenchymal transition of tumor cells
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1.College of Bioengineering, Chongqing University;2.Key Laboratory of Biorheology Science and Technology of Ministry of Education, College of Bioengineering, Chongqing University

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    摘要:

    在肿瘤生长过程中,随着癌细胞的增殖扩张、癌组织胞外基质的重建、周围组织的约束及癌组织间隙液的流动等,肿瘤组织内形成了特殊的应力环境。肿瘤组织不同区域的力学环境和力学特征存在显著的差异,即肿瘤组织的力学异质性。研究发现,肿瘤组织侵袭前沿区域的力学特征更加显著和复杂。特别地,肿瘤细胞的上皮-间质转化(EMT)也偏好集中于该区域,侵袭前沿产生的机械应力可通过TWIST1、TGF-β、WNT等力信号转导途径诱导侵袭前沿肿瘤细胞的EMT,促成肿瘤细胞的侵袭性表型。该文从肿瘤生物力学的角度出发,对肿瘤组织的力学异质性、肿瘤细胞的EMT以及两者间的关系加以综述,为力学微环境靶向的肿瘤治疗提供理论依据。

    Abstract:

    The tumor microenvironment is a dynamic landscape in which the physical and mechanical properties evolve dramatically throughout cancer progression. These changes are driven by enhanced tumor cell contractility and expansion of the growing tumor mass, as well as through alterations to the material properties of the surrounding extracellular matrix (ECM). Consequently, tumor cells are exposed to a number of different mechanical inputs including cell–cell and cell-ECM tension, compression stress, interstitial fluid pressure and shear stress. Obviously, there are significant differences in the mechanical environment and mechanical characteristics of different regions of tumor tissue, that is, mechanical heterogeneity. The study found that the mechanical properties of tumor tissue invasion frontier areas are more significant and complex. In particular, the epithelial-mesenchymal transition (EMT) of tumor cells also prefers to focus on this area, Oncogenes engage signaling pathways that are activated in response to mechanical stress, thereby reworking the cell’s intrinsic response to exogenous mechanical stimuli. The mechanical stress generated by the invasion front can induce EMT of tumor cells through TWIST1, TGF-β, WNT and other force signal transduction pathways, and promote tumor cell invasion. Therefore, this review focuses on the relationship between tumor tissue mechanical heterogeneity and EMT from the perspective of tumor biomechanics, and provides a theoretical basis for mechanoenvironment-targeted therapy of tumors.

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  • 收稿日期:2020-08-03
  • 最后修改日期:2020-09-24
  • 录用日期:2020-09-30
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