The Multiple Roles of CD147 in the Development and Progression of Oral Squamous Cell Carcinoma: An Overview

Abstract

Cluster of differentiation (CD)147, also termed extracellular matrix metalloprotease inducer or basigin, is a glycoprotein ubiquitously expressed throughout the human body, the oral cavity included. CD147 actively participates in physiological tissue development or growth and has important roles in reactive processes such as inflammation, immunity, and tissue repair. It is worth noting that deregulated expression and/or activity of CD147 is observed in chronic inflammatory or degenerative diseases, as well as in neoplasms. Among the latter, oral squamous cell carcinoma (OSCC) is characterized by an upregulation of CD147 in both the neoplastic and normal cells constituting the tumor mass. Most interestingly, the expression and/or activity of CD147 gradually increase as healthy oral mucosa becomes inflamed; hyperplastic/dysplastic lesions are then set on, and, eventually, OSCC develops. Based on these findings, here we summarize published studies which evaluate whether CD147 could be employed as a marker to monitor OSCC development and progression. Moreover, we describe CD147-promoted cellular and molecular events which are relevant to oral carcinogenesis, with the aim to provide useful information for assessing whether CD147 may be the target of novel therapeutic approaches directed against OSCC.

Keywords: CD147; EMT; cancer stem cells; hypoxia; inflammation; oral keratinocytes; oral premalignant diseases; oral squamous cell carcinoma.

Figure 1

CD147 triggering leads to the expression and/or functional activation of proteolytic enzymes, inflammatory mediators, and growth factors with a key role in oral carcinogenesis. Arrows symbolize directions of connections. Abbreviations: AKT, protein kinase B; AP-1, Activator Protein-1; COX-2, cyclooxygenase-2; EGF, epidermal growth factor; EGFR, epidermal growth factor receptor; IC, inflammatory cytokines; MAPK, mitogen-activated protein kinase; MMP, matrix metalloproteinase; NF-kB, Nuclear Factor-kappa B; PGE2, prostaglandin E2; Sp-1, Specificity protein-1; TGFβ, transforming growth β; TGFβR, transforming growth β receptor; uPA, urokinase-like Plasminogen Activator.

Figure 2

CD147 affects OSCC development and progression by modulating epithelial cell viability, growth, motility, and differentiation. Arrows symbolize directions of connections. Abbreviations: AKT, protein kinase B; EGF, epidermal growth factor; EMT, epithelial-to-mesenchymal transition; GLUT, glucose transporter; HIF-1, Hypoxia-inducible factor-1; IC, inflammatory cytokines; MAPK, mitogen-activated protein kinase; MCT, monocarboxylate transporter; MMP, matrix metalloproteinase; SNAI, zinc finger snail homolog; TGFβ, transforming growth β; TWIST, basic helix-loop-helix twist homolog VEGF, vascular endothelial growth factor; ZEB, zinc finger E-box-binding homeobox.