It also helps thedermis function by providing support to the blood vessels, lymphatic vessels,nerves, and gland caps that pass through it to reach the dermis. Subcutaneousfat acts as a shock absorber and heat insulator protecting underlying tissuesfrom cold and mechanical trauma.
Cutaneous squamous cell carcinomas(SCCs) are the second most common and potentiallydeadly human cancers. Asignificant lifetime ultraviolet radiation exposure is the principaldeterminant of squamous cell carcinoma (SCC) and the disease appears mostfrequently in the areas more exposed by natural or artificial sunlight, headand neck among others, such as the edges of the ears, lips, face and scalp.Ultraviolet radiation produces mutations in DNA, usually the formation ofthymidine dimers in the p53 tumor-suppressor gene. Failure to repair thesemutations may result in tumor formation. The solar exposure that a personreceives throughout his life becomes a cumulative damage that can lead to SCCs;the older, the higher the incidence. Chronic skin ulceration and animmunosuppressed state are also predisposing factors for this malignantdisease.
These facts seem to be related by favoring the spread of atypicalkeratinocytes through the epidermis and its subsequent dermal invasion. These solid tumors are complex structures composed ofmultiple cell types in unique microenvironments. Actively proliferating cancercells in SCCs reside in the basal layer of the tumor propagating cancer cells(TPCs), which is located along the tumor stroma interface. In Squamous cellCarcinoma, cells tumor propagating cells are located in the basal layer, incontact with the stroma.
In adult skin, stem cells are located in two differentcompartments, one in the inter-follicullar epidermis (Epi) and the second onein the bulge from the hair follicle (Hair follicle stem cells; HFSC), which arethe most prominent cell population in skin epithelium. TPCs can self-renew to sustain their own identity and differentiate into post-mitotic progeny without tumor propagatingpotential. Differentialgene expressionanalyses uncovereda transcriptional signature,which distinguishesTPCs from normal, adult skin epithelialstem and progenitor cells. Here is where we identify the Oxidative StressResponse as one of the most significantly up-regulated Gene Ontology categoriesin TPCs.
This stress response is triggered by reactive oxygen species (ROS).ROS species are normal byproducts generated through metabolic reactionsessential for eukaryotic organisms. They are associated to aerobic organismsand related to cellular processes such as metabolism, proliferation,differentiation and immune system regulation. These components come from redox reactions generatedprincipally in the mitochondria electronic chain, using oxygen as the principalpathway for ATP production in the process known as oxidativephosphorylation. Nevertheless, they canalso be generated in other cell organelles like peroxisomes, apoplasts andchloroplasts. These oxygen species are composed specially by hydrogen peroxide(H2O2) and free radical’s superoxideanion (O2).