Fromme Julia E, Zigrino Paola
Department of Dermatology and Venereology, University of Cologne, Faculty of Medicine and University Hospital Cologne, Cologne, Germany.
Mildred Scheel School of Oncology Aachen Bonn Cologne Düsseldorf (MSSO ABCD), Cologne, Germany.
Front Mol Biosci. 2022 Apr 26;9:864302. doi: 10.3389/fmolb.2022.864302. eCollection 2022.
The extracellular matrix remodeling in the skin results from a delicate balance of synthesis and degradation of matrix components, ensuring tissue homeostasis. These processes are altered during tumor invasion and growth, generating a microenvironment that supports growth, invasion, and metastasis. Apart from the cellular component, the tumor microenvironment is rich in extracellular matrix components and bound factors that provide structure and signals to the tumor and stromal cells. The continuous remodeling in the tissue compartment sustains the developing tumor during the various phases providing matrices and proteolytic enzymes. These are produced by cancer cells and stromal fibroblasts. In addition to fostering tumor growth, the expression of specific extracellular matrix proteins and proteinases supports tumor invasion after the initial therapeutic response. Lately, the expression and structural modification of matrices were also associated with therapeutic resistance. This review will focus on the significant alterations in the extracellular matrix components and the function of metalloproteinases that influence skin cancer progression and support the acquisition of therapeutic resistance.
皮肤中的细胞外基质重塑源于基质成分合成与降解的微妙平衡，以确保组织稳态。在肿瘤侵袭和生长过程中，这些过程会发生改变，从而产生一个支持生长、侵袭和转移的微环境。除了细胞成分外，肿瘤微环境富含细胞外基质成分和结合因子，它们为肿瘤细胞和基质细胞提供结构和信号。组织隔室中的持续重塑在各个阶段维持肿瘤的发展，提供基质和蛋白水解酶。这些由癌细胞和基质成纤维细胞产生。除了促进肿瘤生长外，特定细胞外基质蛋白和蛋白酶的表达在初始治疗反应后支持肿瘤侵袭。最近，基质的表达和结构修饰也与治疗抗性相关。本综述将聚焦于细胞外基质成分的显著改变以及金属蛋白酶的功能，这些改变影响皮肤癌进展并支持获得治疗抗性。
