4.6 Review

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

Journal

FRONTIERS IN MOLECULAR BIOSCIENCES
Volume 9, Issue -, Pages -

Publisher

FRONTIERS MEDIA SA
DOI: 10.3389/fmolb.2022.864302

Keywords

skin; melanoma; SCC; MCC; BCC; therapy; ECM; TME

Funding

  1. German Cancer Aid through a Mildred Scheel Nachwuchszentrum Grant [70113307]
  2. German Cancer Aid [70114473]

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The remodeling of extracellular matrix and the function of metalloproteinases play a crucial role in the progression of skin cancer and the acquisition of therapeutic resistance.
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.

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