Biology and Development of Skin Cancer
(Wikimedia Commons 2013)
The skin is one of the largest organs in the body, tasked with protecting the body from moisture loss and bacterial invasion, helping maintain body temperature, detoxifying or excreting waste products and toxins, producing vitamin D, providing sensory function, and acting as a reservoir for blood. Structurally, the skin consists of two distinct layers: the outer epidermis is a self-renewing protective layer that is primarily cellular, while the inner dermis is mostly fibrous connective tissue and contains the skin’s vasculature, nerves, hair follicles, and glands. The epidermis consists predominantly of keratinocytes, a cell type formed deep within the epidermis (in a region called the basal layer). In this basal layer, precursor cells (stem cells) actively divide to produce new keratinocytes, which are pushed up to the surface of the skin as new cells are created (Marieb 2009).
As the keratinocytes migrate toward the skin surface, they flatten out (become squamous), fill with the protein keratin, and eventually die. These dead cells, which form the tough outer barrier of the epidermis, are constantly shed and replaced by new cells migrating up from the basal layer. Also within the epidermis are pigmented cells (melanocytes) that give skin its color, immune cells (dendrocytes), and sensory (Merkel) cells (Marieb 2009).
Development of Skin Cancer
Because of their constant exposure to the environment, skin cells are particularly susceptible to the types of damage that can lead to malignant (cancerous) transformation and abnormal cell growth. While the cells at the skin’s surface are shed and replenished quickly, cells in the deeper basal layer (such as the keratinocyte stem cells, melanocytes, or Merkel cells) reside in the epidermis for extended periods of time and can more readily accumulate the necessary genetic damage to become malignant (Thieu 2013).
Sunlight (particularly ultraviolet B [UVB] radiation) is the predominant causative factor catalyst in the malignant transformation of healthy skin cells. UVB radiation can initiate carcinogenesis in several ways. It directly induces breakages in cellular DNA and increases the activity of regulatory T-cells – cells of the immune system that can suppress the skin’s immune response and enable the proliferation of cancer cells (Erb 2008).
UVB radiation also plays a role in preventing the repair and elimination of heavily UV-damaged cells by suppressing the activity of cellular defenses. In several skin cancers, sunlight causes mutations in the p53 gene, which is critical for the protection of genome (DNA) integrity; p53 mutations increase skin cancer risk and have been identified in about 56% of basal cell carcinomas and in >90% of squamous cell carcinomas (Benjamin 2008; Erb 2008). Loss of the protective activities of p53 also enables tumor angiogenesis (the formation of blood vessels to help nourish growing tumors) and metastasis (the spread and establishment of cancer cells in distant organs) (Benjamin 2008). Finally, UV light induces the production of the inflammatory mediator prostaglandin E2 (PGE2) by increasing the activity of the inflammatory enzyme cyclooxygenase-2 (COX-2). Overactivation of the COX-2 enzyme may lead to chronic inflammation which is one of the driving forces behind the development of skin cancer (Rundhaug 2007).