Journal
CELL AND TISSUE RESEARCH
Volume 365, Issue 3, Pages 691-702Publisher
SPRINGER
DOI: 10.1007/s00441-016-2457-z
Keywords
Skin; Squamous cell carcinoma; Matrix metalloproteinase; Eph; Complement
Categories
Funding
- Finnish Cancer Research Foundation
- Sigrid Juselius Foundation
- Turku University Hospital VTR grant [13336]
- Turku University Foundation
- Cancer Foundation Finland sr [140127] Funding Source: researchfish
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Epidermal keratinocyte-derived cutaneous squamous cell carcinoma (cSCC) is the most common metastatic skin cancer, and its incidence is increasing worldwide. Solar UV radiation is an important risk factor for cSCC and leads to genetic and epigenetic changes both in epidermal keratinocytes and dermal cells. Tumor cells in cutaneous cSCCs typically harbor several driver gene mutations, but epidermal keratinocytes in sun-exposed normal skin also contain mutations in these same genes. Therefore, alterations in the microenvironment of premalignant lesions are evidently required for their progression to invasive and metastatic cSCC. For example, alterations in the composition of basement membrane and dermal extracellular matrix are early events in cSCC progression. The presence of microbial structures and the influx of inflammatory cells promote the secretion of proteases, which in turn regulate the availability of growth factors, cytokines, and chemokines and thus influence the growth and invasion of cSCC. Together, these observations emphasize the role of the tumor microenvironment in the progression of cSCC and identify it as a novel therapeutic target in cSCC and other malignant tumors.
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