Faculty of Physics and Earth Science, Institute of Experimental Physics I, Biological Physics Division, University of Leipzig, Linnéstr. 5, 04103 Leipzig, Germany.
Rep Prog Phys. 2014 Jul;77(7):076602. doi: 10.1088/0034-4885/77/7/076602. Epub 2014 Jul 9.
The role of mechanical properties in cancer disease and inflammation is still underinvestigated and even ignored in many oncological and immunological reviews. In particular, eight classical hallmarks of cancer have been proposed, but they still ignore the mechanics behind the processes that facilitate cancer progression. To define the malignant transformation of neoplasms and finally reveal the functional pathway that enables cancer cells to promote cancer progression, these classical hallmarks of cancer require the inclusion of specific mechanical properties of cancer cells and their microenvironment such as the extracellular matrix as well as embedded cells such as fibroblasts, macrophages or endothelial cells. Thus, this review will present current cancer research from a biophysical point of view and will therefore focus on novel physical aspects and biophysical methods to investigate the aggressiveness of cancer cells and the process of inflammation. As cancer or immune cells are embedded in a certain microenvironment such as the extracellular matrix, the mechanical properties of this microenvironment cannot be neglected, and alterations of the microenvironment may have an impact on the mechanical properties of the cancer or immune cells. Here, it is highlighted how biophysical approaches, both experimental and theoretical, have an impact on the classical hallmarks of cancer and inflammation. It is even pointed out how these biophysical approaches contribute to the understanding of the regulation of cancer disease and inflammatory responses after tissue injury through physical microenvironmental property sensing mechanisms. The recognized physical signals are transduced into biochemical signaling events that guide cellular responses, such as malignant tumor progression, after the transition of cancer cells from an epithelial to a mesenchymal phenotype or an inflammatory response due to tissue injury. Moreover, cell adaptation to mechanical alterations, in particular the understanding of mechano-coupling and mechano-regulating functions in cell invasion, appears as an important step in cancer progression and inflammatory response to injuries. This may lead to novel insights into cancer disease and inflammatory diseases and will overcome classical views on cancer and inflammation. In addition, this review will discuss how the physics of cancer and inflammation can help to reveal whether cancer cells will invade connective tissue and metastasize or how leukocytes extravasate and migrate through the tissue. In this review, the physical concepts of cancer progression, including the tissue basement membrane a cancer cell is crossing, its invasion and transendothelial migration as well as the basic physical concepts of inflammatory processes and the cellular responses to the mechanical stress of the microenvironment such as external forces and matrix stiffness, are presented and discussed. In conclusion, this review will finally show how physical measurements can improve classical approaches that investigate cancer and inflammatory diseases, and how these physical insights can be integrated into classical tumor biological approaches.
机械性能在癌症疾病和炎症中的作用在许多肿瘤学和免疫学综述中仍未得到充分研究，甚至被忽视。特别是，已经提出了癌症的八个经典特征，但它们仍然忽略了促进癌症进展的过程背后的力学。为了定义肿瘤的恶性转化，并最终揭示使癌细胞能够促进癌症进展的功能途径，这些癌症的经典特征需要包括癌细胞及其微环境（如细胞外基质）以及嵌入细胞（如成纤维细胞、巨噬细胞或内皮细胞）的特定机械特性。因此，本综述将从生物物理的角度呈现当前的癌症研究，因此将重点介绍研究癌细胞侵袭性和炎症过程的新物理方面和生物物理方法。由于癌症或免疫细胞嵌入细胞外基质等特定微环境中，因此不能忽略该微环境的机械性能，并且微环境的改变可能会对癌症或免疫细胞的机械性能产生影响。在这里，强调了生物物理方法（实验和理论）如何影响癌症和炎症的经典特征。甚至指出这些生物物理方法如何通过物理微环境特性感应机制促进对组织损伤后癌症疾病和炎症反应的调节的理解。通过从上皮细胞向间充质表型的转变或组织损伤引起的炎症反应，识别物理信号被转导为指导细胞反应的生化信号事件，如恶性肿瘤进展。此外，细胞对机械改变的适应，特别是对细胞侵袭中的机械偶联和机械调节功能的理解，似乎是癌症进展和对损伤的炎症反应的重要步骤。这可能会为癌症疾病和炎症性疾病提供新的见解，并克服对癌症和炎症的经典观点。此外，本综述将讨论癌症和炎症的物理学如何帮助揭示癌细胞是否会侵入结缔组织并转移，或者白细胞如何通过组织渗出和迁移。在本综述中，呈现并讨论了癌症进展的物理概念，包括癌细胞正在穿过的组织基底膜、其侵袭和穿内皮迁移以及炎症过程的基本物理概念和细胞对微环境机械应力（如外力和基质刚度）的反应。总之，本综述最终将展示物理测量如何改进研究癌症和炎症性疾病的经典方法，以及这些物理见解如何整合到经典的肿瘤生物学方法中。
