Hypothesis: Overexpression or overactivation of PAR-2 might be involved in the evolution of basal cell carcinoma
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https://doi.org/10.5070/D34f13g0tzMain Content
Hypothesis: Overexpression or overactivation of PAR-2 might be involved in the evolution of basal cell carcinoma
MR Namazi MD
Dermatology Online Journal 9 (5): 32
From the Dermatology Department, Shiraz University of Medical Sciences, Shiraz, Iran. namazi_mr@yahoo.com
Proteinase-activated receptor-2 (PAR-2) is a seven-transmembrane G-protein-coupled receptor that is activated by serine-protease cleavage and is present in numerous cell types including keratinocytes [1]. PAR-2 is believed to regulate the transfer of melanosomes from melanocytes to keratinocytes [2], and to inhibit keratinocyte proliferation and differentiation [3]. It has been suggested that PAR-2 may play a role in regulation of some forms of cancer, such as stomach and colon carcinomas [1].
Basal cell carcinoma (BCC) is a common, very slowly growing, locally invasive tumor that rarely metastasizes [4]. It has been shown that, in addition to being undifferentiated, BCC has a low rate of proliferation. The duration of the S phase in BCC is significantly longer than in normal epidermis (about 19 hours vs. 16 hours for normal epidermis). This observation is contrary to what is seen in some animal-tumor systems, in which all parts of the cell cycle are shortened in the neoplastic cell population compared to its normal counterpart [4, 5].
Given that PAR-2 inhibits keratinocyte proliferation and differentiation, and that BCC shows low differentiation and proliferation parameters, PAR-2 overexpression or its overactivation by pathophysiological levels of PAR-2 activators, might have a role in the evolution of BCC. This especially may be the case in pigmented BCC, which shows extremely low proliferation rate as well as hyperpigmention [6]; the two phenomena explicable by PAR-2 overstimulation or overexpression.
Investigative studies on this hypothesis are warranted.
References
1. Macfarlane SR, Seather MJ, Kanke T, Hunter GD, Plevin R. Proteinase-activated receptors. Pharmacol Rev 2001; 53(2): 245-82.2. Seiberg M, Paine C, Sharlow E, C. Stanzo M, Andrade-Gordon P, Eisinger M, et al. PAR-2 regulated pigmentation via keratinocyte-melanocyte interactions. Exp Cell Res 2000; 254: 25-32.
3. Derian CK, Eckardt AJ, Andrade Gordon P. Differential regulation of human keratinocyte growth and differentiation by a novel family of protease activated receptors. Cell Growth Differen 1997; 8: 743-9.
4. Weinstein GD, Frost P. Cell proliferation in human basal cell carcinoma. Cancer Res 1970; 30: 724-8.
5. Moretti G, Cardo P, Rampini E, Pellerano S. Testosterone metabolism in basal cell epitheliomas. J Invest Dermatol 1978; 7: 361-2.
6. Odom RB, James WD, Berger TG. Andrews' Diseases of the Skin, 9th edn. Philidalphia: W.B. Saunders, 2000: 822.
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