Proteases in Melanoma

Zigrino, Paola; Mauch, Cornelia

doi:10.1007/978-3-319-41319-8_8

Cited by 2 publications

(2 citation statements)

References 114 publications

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“…This allows cells to proteolytically process different ECM components, rearrange them, release bound growth factors and cellular bonds to invade the underlying tissue. Several matrix metalloproteinases are expressed in melanoma, the tumor, and the peritumoral stroma, including MMP-1, MMP-2, MMP-9, MMP-13, and MMP-14 ( Zigrino and Mauch, 2017 ). Shaverdashvili et al (2014 ) demonstrate in vivo that melanoma cells expressing MMP-14 activate MMP-2, thereby maintaining RAC1 activity and promoting the invasive capacity of melanoma cells.…”

Section: Ecm and Remodeling Enzymes In The Progression Of Skin Cancersmentioning

confidence: 99%

“…Corruption of this highly dynamic process leads to altered balance that underlies the pathogenesis and progression of many diseases ( Winkler et al, 2020 ). Matrix metalloproteinases (MMPs) have critical roles in this process, and imbalanced activity is implicated in the pathogenesis and progression of many skin diseases, e.g., inflammatory diseases, healing defects, fibrosis, and cancer ( Zigrino and Mauch, 2017 ).…”

Section: Introductionmentioning

confidence: 99%

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

Fromme

Zigrino

2022

Front. Mol. Biosci.

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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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Section: Ecm and Remodeling Enzymes In The Progression Of Skin Cancersmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

Fromme

Zigrino

2022

Front. Mol. Biosci.

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Fibroblast MMP14-Dependent Collagen Processing Is Necessary for Melanoma Growth

Pach

Brinckmann

Rübsam

et al. 2021

Cancers

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Skin homeostasis results from balanced synthesis and degradation of the extracellular matrix in the dermis. Deletion of the proteolytic enzyme MMP14 in dermal fibroblasts (MMP14Sf−/−) leads to a fibrotic skin phenotype with the accumulation of collagen type I, resulting from impaired proteolysis. Here, we show that melanoma growth in these mouse fibrotic dermal samples was decreased, paralleled by reduced tumor cell proliferation and vessel density. Using atomic force microscopy, we found increased peritumoral matrix stiffness of early but not late melanomas in the absence of fibroblast-derived MMP14. However, total collagen levels were increased at late melanoma stages in MMP14Sf−/− mice compared to controls. In ex vivo invasion assays, melanoma cells formed smaller tumor islands in MMP14Sf−/− skin, indicating that MMP14-dependent matrix accumulation regulates tumor growth. In line with these data, in vitro melanoma cell growth was inhibited in high collagen 3D spheroids or stiff substrates. Most importantly, in vivo induction of fibrosis using bleomycin reduced melanoma tumor growth. In summary, we show that MMP14 expression in stromal fibroblasts regulates melanoma tumor progression by modifying the peritumoral matrix and point to collagen accumulation as a negative regulator of melanoma.

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Proteases in Melanoma

Cited by 2 publications

References 114 publications

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

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

Fibroblast MMP14-Dependent Collagen Processing Is Necessary for Melanoma Growth

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