Adhesion Molecules in Non-melanoma Skin Cancers: A Comprehensive Review

Abstract

Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) are the most frequently diagnosed cancers, generating significant medical and financial problems. Cutaneous carcinogenesis is a very complex process characterized by genetic and molecular alterations, and mediated by various proteins and pathways. Cell adhesion molecules (CAMs) are transmembrane proteins responsible for cell-to-cell and cell-to-extracellular matrix adhesion, engaged in all steps of tumor progression. Based on their structures they are divided into five major groups: cadherins, integrins, selectins, immunoglobulins and CD44 family. Cadherins, integrins and CD44 are the most studied in the context of non-melanoma skin cancers. The differences in expression of adhesion molecules may be related to the invasiveness of these tumors, through the loss of tissue integrity, neovascularization and alterations in intercellular signaling processes. In this article, each group of CAMs is briefly described and the present knowledge on their role in the development of non-melanoma skin cancers is summarized.Non-melanoma skin cancers (NMSC) are the most frequently diagnosed malignancies and their prevalence has increased dramatically over the last 30 years. Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) represent 99% of all NMSC. BCC, which constitutes 70% of NMSC develops from basal epithelial cells of hair follicles or pluripotent epidermal basal cells and has a metastatic rate of only 0.0028-0.05% (1). Depending on the different features of tumor cells, there are many histological types of BCC, with different, but still low metastatic potential (2). SCC develops from the proliferating squamous layer of the epidermis, shows a metastatic rate of 0,1-9,9% and contributes to approximately 75% of deaths due to NMSC (3, 4). Although both skin cancers generally have a good prognosis, due to their high prevalence, they generate significant medical and financial problems worldwide. The most important risk factor of NMSC is exposure to the ultraviolet radiation, and both ultraviolet (UV) B and UVA play crucial roles in skin carcinogenesis affecting every stage, including direct cellular damage, production of reactive oxygen species, DNA alterations, and impairment of cell-mediated immune response (5).A wide variety of risk factors of NMSC is known, such as Fitzpatrick I and II skin phototypes, age over 50 years, family history of skin cancers, chronic immunosuppression, long-lasting ulceration, and scars. In addition, exposure to carcinogenic substances, like arsenic and tobacco, HPV viruses, actinic keratosis, and chronic dermatoses, including lichen sclerosus, lupus erythematosus, and lichen planus, are associated with a higher risk of SCC (6).Carcinogenesis is a very complex process; it is mediated by various proteins and pathways and characterized by genetic and molecular alterations. Changes in the expression or function of cell adhesion molecules (CAM) are involved in all steps of the progression of the malignancy, starting from the detachm...

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“…Together with SCC, BCC incidence is increasing worldwide, representing about 95% of the total NMSC, with a generally good prognosis, especially if recognized early [ 33 , 46 ]. Despite skin cancer pathogenesis is multifactorial, UV radiations, in particular UVB, are historically recognized to be one of the main risk factors for skin carcinogenesis [ 47 ].…”

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“…Notably, these adhesion genes are connected with angiogenesis and immune response modulation, suggesting a potential integration of broad responses. Upregulated genes included the cell adhesion molecules Icam1, Itga4, and Selp, whereas Itga2 was downregulated [54] (Figure 3B). Additionally, the transcriptome showed increased expression of the extracellular matrix proteins Wisp1, Cyr61, Lgal3bp, Nid1, Lama4, Col5a3, and Tinagl1 [55][56][57][58].…”

“…Cell adhesion in carcinogenesis is positively and negatively regulated, enabling cancer cells to attach to other cells and the extracellular matrix, favoring their permanence at the CSC niche or their migration and dissemination to distant sites [54]. The actin cytoskeleton plays a critical role in cell adhesion and migration.…”

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