Matrix metalloproteinases in keratinocyte carcinomas.

Area of Science:

• Oncology
• Dermatology
• Cancer Biology

Background:

• Global incidence of keratinocyte-derived cancers, including basal cell carcinoma (BCC) and cutaneous squamous cell carcinoma (cSCC), is increasing.
• BCC is the most common malignancy worldwide, while cSCC is the most frequent metastatic skin cancer.
• There is a growing need for novel therapeutic strategies for unresectable/metastatic cSCC and aggressive BCC subtypes.

Purpose of the Study:

• To investigate the role of the tumor microenvironment in the progression of cSCC and aggressive BCC.
• To identify potential therapeutic targets within the tumor microenvironment for these skin cancers.

Main Methods:

• Analysis of genetic and epigenetic alterations in keratinocytes induced by UV radiation.
• Examination of changes in basement membrane and dermal extracellular matrix composition.
• Investigation of the roles of inflammatory cells, stromal fibroblasts, and their secreted factors (e.g., MMPs, TGF-β, KGF).

Main Results:

• Solar UV radiation is a key risk factor, causing alterations in keratinocytes and the tumor microenvironment.
• Activated fibroblasts promote inflammation and matrix metalloproteinase (MMP) production, facilitating cSCC invasion.
• Cross-talk between tumor cells and fibroblasts, involving factors like TGF-β and KGF, influences cSCC progression and invasiveness.

Conclusions:

• The interplay between tumor and stromal cells is crucial for the progression of cSCC and BCC.
• The tumor microenvironment represents a promising therapeutic target for cSCC and aggressive BCC subtypes.