Mierke Claudia T
Faculty of Physics and Earth Science, Institute of Experimental Physics I, Soft Matter Physics Division, University of Leipzig, Leipzig, Germany.
Mol Biosyst. 2012 Jun;8(6):1639-49. doi: 10.1039/c2mb25024a. Epub 2012 Apr 13.
Most cancer-related deaths are caused by the ability of cancer cells to metastasize. This process includes the dissemination of cancer cells from the primary tumor side and their migration to targeted organ sites. During the migration of cancer cells through the connective tissue microenvironment, which consists of endothelial cells and extracellular matrix components, biomechanical properties are crucial for the efficiency and speed of cancer cell invasion and subsequently, metastases formation. Biomechanics can enable cancer cells to migrate through tissue, transmigrate through basement membranes as well as endothelial monolayers and form metastases in targeted organs. The current focus of cancer research still lies on the investigation of cancer cell's biochemical and molecular capabilities such as molecular genetics and gene signaling, but these approaches ignore the mechanical nature of the invasion process of cancer cells. Moreover, even the role of the endothelium during the transmigration and invasion of cells is not clear, it has been seen as a passive barrier, but this could not explain all novel findings. This review discusses how cancer cells alter the structural, biochemical and mechanical properties of the endothelium to regulate their own invasiveness through extracellular matrices and hence, through the tissue microenvironment. Finally, this review sheds light on the mechanical properties of cancer cells and the interacting endothelium and points out the importance of the mechanical properties as a critical determinant for the efficiency of cancer cell invasion and the overall progression of cancer. In conclusion, the regulation of the endothelial cell's biomechanical properties by cancer cells is a critical determinant of cancer cell invasiveness and may affect the future development of new cancer treatments.
大多数与癌症相关的死亡是由癌细胞的转移能力引起的。这个过程包括癌细胞从原发肿瘤部位扩散并迁移到目标器官部位。在癌细胞通过由内皮细胞和细胞外基质成分组成的结缔组织微环境迁移的过程中，生物力学特性对于癌细胞侵袭的效率和速度以及随后转移灶的形成至关重要。生物力学可以使癌细胞穿过组织，穿过基底膜以及内皮单层，并在目标器官中形成转移灶。目前癌症研究的重点仍然在于研究癌细胞的生化和分子能力，如分子遗传学和基因信号传导，但这些方法忽略了癌细胞侵袭过程的机械本质。此外，即使内皮细胞在细胞迁移和侵袭过程中的作用也不清楚，它一直被视为一个被动屏障，但这无法解释所有新发现。这篇综述讨论了癌细胞如何改变内皮细胞的结构、生化和机械特性，以通过细胞外基质，进而通过组织微环境来调节自身的侵袭性。最后，这篇综述阐明了癌细胞和相互作用的内皮细胞的机械特性，并指出机械特性作为癌细胞侵袭效率和癌症整体进展的关键决定因素的重要性。总之，癌细胞对内皮细胞生物力学特性的调节是癌细胞侵袭性的关键决定因素，可能会影响新癌症治疗方法的未来发展。
