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.

About a Possible Impact of Endodontic Infections by Fusobacterium nucleatum or Porphyromonas gingivalis on Oral Carcinogenesis: A Literature Overview

“…Additional pro-inflammatory mediators produced by the leukocytes upon their arrival in the injured oral tissue include IL-1 and IL-8 [5,6,65].…”

“…Apart from the leukocytes, the inflamed oral tissue is infiltrated by fibroblasts directed at repairing the damaged tissue [65]. Those fibroblasts synthesize the transforming growth factor (TGF)-β1, while nearby macrophages release the epidermal growth factor (EGF) [66]: both types of cytokines deeply influence the proliferation and differentiation of epithelial cells [66].…”

“…It is noteworthy that the pro-inflammatory IL-1, IL-6, IL-8, and TNFα, as well as TGF-β1 and EGF, are almost absent from the healthy oral cavity, are found at low levels in periodontitis, are upregulated in OPMDs, and are expressed at even higher levels in OSCCs [65,66], especially when F. nucleatum and/or P. gingivalis are present [5,6].…”

Receptors and Cofactors That Contribute to SARS-CoV-2 Entry: Can Skin Be an Alternative Route of Entry?

“…CD147 is widely expressed in human tissues and exhibits heterogeneous glycosylation between tissues and cell types. It is upregulated in chronically inflamed mucosa and in cancer [ 83 ]. Importantly, CD147 expression is regulated by various transcription factors, miRNA and soluble mediators in different physiological, pathological and tissue-specific contexts.…”

“…CD147 is expressed by keratinocytes, immune cells and upregulated in psoriatic skin lesions [ 145 , 157 ]. CD147 expression can be induced by cytokines such as IL-22, IL-1α, TGF-β1 or growth factors such as EGF [ 83 , 157 , 158 ]. As CD147 is a receptor mediating cellular entry of all the variants of SARS-CoV-2, it may play a preponderant role in the skin where it is highly expressed.…”