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Nothing to sneeze at: Histamine and histamine receptors in oral carcinogenesis
Author(s) -
Salem Abdelhakim,
Salo Tuula
Publication year - 2021
Publication title -
oral diseases
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.953
H-Index - 87
eISSN - 1601-0825
pISSN - 1354-523X
DOI - 10.1111/odi.13411
Subject(s) - histamine , histamine receptor , histamine h4 receptor , medicine , cancer , autocrine signalling , paracrine signalling , malignancy , receptor , carcinogenesis , immunology , cancer research , histamine h2 receptor , antagonist
Abstract Oral squamous cell carcinoma (OSCC), the most common oral malignancy, shows an increasing rate of incidence worldwide. In spite of the recent advances in cancer research, OSCC therapy continues to have unfavourable outcomes, and thus, patient's prognosis remains relatively poor. Current research has been devoted to identifying novel therapeutic targets also in the tumour microenvironment (TME). Histamine and its G‐protein‐coupled receptors (H1R‐H4R) play vital roles in multiple cancer‐associated processes in TME, where histamine is mainly produced by mast cells. However, oral epithelial cells were recently shown to produce low concentrations of histamine in autocrine and paracrine modes. These findings, together with the discovery of the high‐affinity histamine H4 receptor, have led to a massive increase in our understanding of histamine functions. In this review, we aim to summarize the most recent findings regarding histamine and its receptors and their involvement in oral carcinogenesis—from oral potentially malignant disorders (OPMDs) to invasive OSCC. Importantly, histamine receptors are differentially expressed in OPMDs and OSCC. Furthermore, H1R and H4R are associated with clinicopathological characteristics of OSCC patients, suggesting a role in prognosis. Due to the enormous success of histamine‐based medications, histamine receptors may also represent promising and viable drug targets in oral cancer.