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Physical traits of cancer
Science ( IF 56.9 ) Pub Date : 2020-10-29 , DOI: 10.1126/science.aaz0868
Hadi T Nia 1, 2 , Lance L Munn 1 , Rakesh K Jain 1, 3
Affiliation  

Physical traits of cancer The biological and physical properties of tumors contribute to their growth and to treatment outcome. Although intense research efforts have helped to delineate cancer biology, the physics of cancer has only emerged in relatively recent times as a key area of research. Nia et al. reviewed the physical features that are common to tumors and that limit successful treatment: solid stresses, interstitial fluid pressure, stiffness (rigidity), and architecture and organization of tumor constituents. The authors provide a conceptual framework and discuss the origins of these distinct physical traits of cancer and how they enable and synergize with aberrant cancer biology to fuel cancer initiation, progression, immune evasion, and treatment resistance. Science, this issue p. eaaz0868 BACKGROUND Historically, cancer has been considered a disease of the cell, caused by mutations in genes that control proliferation, differentiation, and death. In recent decades, however, the microenvironment surrounding the cancer cell has gained notoriety as a coconspirator in tumor initiation, progression, immune evasion, and treatment response. As tumors grow, they disrupt the structure and function of the surrounding tissue via physical and biochemical mechanisms. The resulting physical abnormalities affect both cancer cells and their microenvironment and fuel tumorigenesis and treatment resistance. The links between cancer biology and physics have provided opportunities for the discovery of new drugs and treatment strategies. ADVANCES Here, we propose four distinct physical cancer traits that capture the biomechanical abnormalities in tumors: (i) elevated solid stress, (ii) elevated interstitial fluid pressure, (iii) increased stiffness and altered material properties, and (iv) altered tissue microarchitecture. Solid stresses are created as proliferating and migrating cells push and stretch solid components of the surrounding tissue. Being distinct from fluid pressure and close to zero in most normal tissues, solid stresses are large enough to compress blood and lymphatic vessels in and around tumors, impairing blood flow and the delivery of oxygen, drugs, and immune cells. Acting at organ, tissue, and cellular levels, solid stresses activate signaling pathways that promote tumorigenesis and invasiveness and induce treatment resistance. Elevated interstitial fluid pressure is caused by leakage of plasma from abnormally permeable tumor blood vessels and insufficient lymphatic drainage. As a result, the interstitial fluid leaks out of the tumor into the peritumor tissue, causing edema and elution of drugs and growth factors and facilitating invasion and metastasis through flow-induced shear stresses. Increased stiffness is caused by matrix deposition and remodeling. Traditionally used as a diagnostic marker, and more recently as a prognostic factor, increased stiffness activates signaling pathways that promote proliferation, invasiveness, and metastasis of cancer cells. Finally, when normal tissue architecture is disrupted by cancer growth and invasion, microarchitecture is altered. Stromal and cancer cells and extracellular matrix adopt new organization. This changes the interactions between an individual cell and its surrounding matrix and cells, which affects signaling pathways associated with invasion and metastasis. OUTLOOK The tumor microenvironment is characterized by both biological and physical abnormalities. The growing appreciation of the role of tumor-stromal interactions in cancer has led to seminal discoveries that have resulted in previously unexplored targets and strategies for treatment. Understanding the key principles underlying the origins and consequences of the physical traits of cancer will be critical for improving treatment. Many of the concepts involved are nonintuitive and require deep and broad understanding of both the physical and biological aspects of cancer. Therefore, a rigorous but accessible description of physical cancer traits will assist research into the physical sciences of cancer—a highly multidisciplinary area—and help it remain an active and progressive subfield of cancer research. Physical traits of cancer. To provide a comprehensive framework for understanding the links between the physics of cancer and signaling pathways in cancer biology in terms of a small number of underlying principles, we propose four physical traits of cancer that characterize the major physical abnormalities shared by most if not all tumors. The role of the physical microenvironment in tumor development, progression, metastasis, and treatment is gaining appreciation. The emerging multidisciplinary field of the physical sciences of cancer is now embraced by engineers, physicists, cell biologists, developmental biologists, tumor biologists, and oncologists attempting to understand how physical parameters and processes affect cancer progression and treatment. Discoveries in this field are starting to be translated into new therapeutic strategies for cancer. In this Review, we propose four physical traits of tumors that contribute to tumor progression and treatment resistance: (i) elevated solid stresses (compression and tension), (ii) elevated interstitial fluid pressure, (iii) altered material properties (for example, increased tissue stiffness, which historically has been used to detect cancer by palpation), and (iv) altered physical microarchitecture. After defining these physical traits, we discuss their causes, consequences, and how they complement the biological hallmarks of cancer.

中文翻译:

癌症的生理特征

癌症的物理特性 肿瘤的生物学和物理特性有助于它们的生长和治疗结果。尽管密集的研究工作有助于描绘癌症生物学,但癌症物理学只是在相对较新的时期才成为一个关键的研究领域。尼亚等人。回顾了肿瘤常见且限制成功治疗的物理特征:固体应力、组织间液压力、刚度(刚性)以及肿瘤成分的结构和组织。作者提供了一个概念框架,并讨论了癌症这些不同物理特征的起源,以及它们如何促成异常癌症生物学并与之协同作用,以促进癌症的发生、进展、免疫逃避和治疗抵抗。科学,这个问题 p。eaaz0868 背景历史上,癌症被认为是一种细胞疾病,由控制增殖、分化和死亡的基因突变引起。然而,近几十年来,癌细胞周围的微环境作为肿瘤发生、进展、免疫逃避和治疗反应的共谋而臭名昭著。随着肿瘤的生长,它们会通过物理和生化机制破坏周围组织的结构和功能。由此产生的身体异常会影响癌细胞及其微环境,并助长肿瘤发生和治疗抵抗。癌症生物学和物理学之间的联系为发现新药物和治疗策略提供了机会。进展在这里,我们提出了四种不同的物理癌症特征,可以捕捉肿瘤中的生物力学异常:(i) 固体应力升高,(ii) 间质流体压力升高,(iii) 刚度增加和材料特性改变,以及 (iv) 组织微结构改变。当增殖和迁移的细胞推动和拉伸周围组织的固体成分时,会产生固体应力。与流体压力不同并且在大多数正常组织中接近于零,固体压力大到足以压缩肿瘤内部和周围的血液和淋巴管,损害血液流动以及氧气、药物和免疫细胞的输送。固体应激作用于器官、组织和细胞水平,激活信号通路,促进肿瘤发生和侵袭并诱导治疗抵抗。升高的间质液压力是由异常通透性肿瘤血管中的血浆渗漏和淋巴引流不足引起的。结果,间质液从肿瘤渗漏到肿瘤周围组织,引起水肿和药物和生长因子的洗脱,并通过流动诱导的剪切应力促进侵袭和转移。增加的刚度是由基质沉积和重塑引起的。传统上用作诊断标志物,最近用作预后因素,增加的刚度会激活促进癌细胞增殖、侵袭和转移的信号通路。最后,当正常组织结构被癌症生长和侵袭破坏时,微结构就会改变。基质细胞和癌细胞以及细胞外基质采用新的组织。这会改变单个细胞与其周围基质和细胞之间的相互作用,从而影响与侵袭和转移相关的信号通路。展望 肿瘤微环境的特点是生物学和物理异常。对肿瘤间质相互作用在癌症中的作用的日益认识导致了开创性的发现,这些发现导致了以前未探索过的治疗靶点和策略。了解癌症物理特征的起源和后果的关键原则对于改善治疗至关重要。所涉及的许多概念并不直观,需要对癌症的物理和生物学方面有深入而广泛的了解。因此,对癌症物理特征的严格但易于理解的描述将有助于癌症物理科学的研究——一个高度多学科的领域——并帮助它保持癌症研究的一个活跃和进步的子领域。癌症的生理特征。为了提供一个全面的框架,根据少数基本原理来理解癌症物理学与癌症生物学信号通路之间的联系,我们提出了癌症的四个物理特征,这些特征表征了大多数(如果不是所有)肿瘤共有的主要物理异常. 物理微环境在肿瘤发展、进展、转移和治疗中的作用越来越受到重视。癌症物理科学这一新兴的多学科领域现在被工程师、物理学家、细胞生物学家、发育生物学家、肿瘤生物学家和肿瘤学家所接受,他们试图了解物理参数和过程如何影响癌症进展和治疗。该领域的发现开始转化为新的癌症治疗策略。在本次审查中,我们提出了有助于肿瘤进展和治疗抵抗的肿瘤的四个物理特征:(i)固体应力升高(压缩和张力),(ii)间质液压力升高,(iii)改变的材料特性(例如,增加的组织刚度,历史上曾用于通过触诊检测癌症),以及 (iv) 改变了物理微结构。在定义了这些身体特征之后,我们讨论了它们的原因、后果以及它们如何补充癌症的生物学特征。历史上曾用于通过触诊检测癌症),以及 (iv) 改变了物理微结构。在定义了这些身体特征之后,我们讨论了它们的原因、后果以及它们如何补充癌症的生物学特征。历史上曾用于通过触诊检测癌症),以及 (iv) 改变了物理微结构。在定义了这些身体特征之后,我们讨论了它们的原因、后果以及它们如何补充癌症的生物学特征。
更新日期:2020-10-29
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