Environment and Skin by Jean Krutmann & Hans F. Merk

Author:Jean Krutmann & Hans F. Merk
Language: eng
Format: epub
Publisher: Springer International Publishing, Cham

During the second stage of photocarcinogenesis, termed promotion, repeated doses of UV induce chronic inflammation and encourage clonal expansion of initiated cells. Chronic inflammation is a predisposing factor for cancer promotion, as evidenced by an increased incidence of cancers in patients with chronic inflammatory conditions, such as reflux esophagitis, chronic hepatitis, chronic H. pylori infection, and inflammatory bowel disease [25]. The UV response, defined as the genes and signaling cascades activated by UVB, is a pseudo-growth response that mirrors the growth response triggered by mitogens. The UV response is initiated in both the nucleus via photoproduct formation and in the cytoplasm. UV-induced activation of signaling pathways in the cytoplasm induces activation of transcription factors: nuclear factor κ-light-chain-enhancer of activated B cells (NF-κB) and activator protein 1 (AP-1). The resulting changes in gene expression are responsible for chronic inflammation and increased proliferation. The end result is a premalignant actinic keratosis (AK, also known as solar keratosis), a reversible premalignant lesion. Five to twenty percentage of AKs progress into SCCs in 10–25 years in humans [26].

During progression, the third stage of photocarcinogenesis, with continued sun exposure, premalignant AKs undergo changes that grant genetic instability and lead to changes frequently observed in cancerous cells, such as acquired chromosomal aberrations. A key event during progression is epithelial-mesenchymal transition (EMT), in which epithelial cells undergo alterations in adhesion, cellular architecture, and morphology to remodel the extracellular matrix and increase their greater migratory capacity [27]. The induction of angiogenesis by proangiogenic cytokines, augmented production of cyclooxygenase-2 (COX-2), and increased synthesis of vascular endothelial growth factor (VEGF) are also essential during this stage. The end product of progression is an invasive squamous cell carcinoma.

UV-induced defects in immunological surveillance also contribute to the development of skin cancer. Immunological defense mechanisms have evolved that neutralize and/or eliminate malignant cells before they can become clinically apparent tumors. UV exposure inactivates these immunological defenses, thereby allowing neoplastic cells to grow and develop into invasive skin cancers.

Fortunately, progressing through all three stages of photocarcinogenesis usually takes years to decades. It is important to emphasize that while BCC and SCC both arise from keratinocytes and the vast majority are caused by UVR, they are quite different in their pathogenesis and behavior. BCCs are believed to develop de novo without a precursor lesion and can be locally invasive, but are almost never metastatic.

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