AUTHOR=Fromme Julia E. , Zigrino Paola 

TITLE=The Role of Extracellular Matrix Remodeling in Skin Tumor Progression and Therapeutic Resistance

JOURNAL=Frontiers in Molecular Biosciences

VOLUME=Volume 9 - 2022

YEAR=2022

URL=https://www.frontiersin.org/journals/molecular-biosciences/articles/10.3389/fmolb.2022.864302

DOI=10.3389/fmolb.2022.864302

ISSN=2296-889X

ABSTRACT=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 matrices and bound factors that provide structure and signals to the tumor and stromal cells. The continuous remodeling in this tissue compartment sustains the developing tumor during the various phases providing matrices and proteolytic enzymes. These are produced by cancer cells and stromal fibroblasts. Besides fostering tumor growth, the expression of specific ECM proteins and proteinases supports tumor invasion after the initial therapeutic response. Lately, expression and structural modification of matrices were associated with therapeutic resistance. This review will focus on the significant alterations in the ECM and the function of metalloproteinases that influence skin cancer progression and support the acquisition of therapeutic resistance.