University of Oulu

Salem, A, Salo, T. Nothing to sneeze at: Histamine and histamine receptors in oral carcinogenesis. Oral Dis. 2021; 27: 1090– 1096.

Nothing to sneeze at : histamine and histamine receptors in oral carcinogenesis

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Author: Salem, Abdelhakim1,2; Salo, Tuula1,3,4,5,6
Organizations: 1Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Helsinki, Finland
2Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, Helsinki, Finland
32Translational Immunology Research Program (TRIMM), Research Program Unit (RPU), University of Helsinki, Helsinki, Finland
4Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland
5Oulu University Hospital, Oulu, Finland
6Helsinki University Hospital (HUS), Helsinki, Finland
Format: article
Version: published version
Access: open
Online Access: PDF Full Text (PDF, 0.5 MB)
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Language: English
Published: John Wiley & Sons, 2021
Publish Date: 2020-06-17


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.

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Series: Oral diseases
ISSN: 1354-523X
ISSN-E: 1601-0825
ISSN-L: 1354-523X
Volume: 27
Issue: 5
Pages: 1090 - 1096
DOI: 10.1111/odi.13411
Type of Publication: A2 Review article in a scientific journal
Field of Science: 3122 Cancers
Funding: The authors would like to acknowledge the funders of this work: Emil Aaltonen Foundation (Emil Aaltosen säätiö);The Jane and Aatos Erkko Foundation; The Maud Kuistila Memorial Foundation; K. Albin Johanssonin säätiö; and Helsinki University Central Hospital (HUS) Research Funds.
Copyright information: © 2020 The Authors. Oral Diseases published by John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.