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.
Highlights
Cancer continues to be a leading cause of death and the most crucial hurdle to extend life expectancy in the current century (Bray et al, 2018)
Oral squamous cell carcinoma (OSCC) is the most common oral malignancy, which accounts for about 90% of all malignant neoplasms of the oral cavity (Johnson, Jayasekara, & Amarasinghe, 2011)
The involvement of histamine and histamine receptors in different types of cancer has been extensively summarized in several comprehensive reviews (Kennedy, Hodges, Meng, Alpini, & Francis, 2012; Massari et al, 2020; Nicoud, Formoso, & Medina, 2019). In this minireview, we aim to focus on the current knowledge regarding histamine and histamine receptors and their potential role in oral carcinogenesis
Summary
Cancer continues to be a leading cause of death and the most crucial hurdle to extend life expectancy in the current century (Bray et al, 2018). Histamine has been exploited in medicine since 1930s, ligands targeting H1R-H3R remain, by and large, ineffective in treating many immune-associated diseases and cancer Such limitation has been attributed to the substantial variations in the extracellular levels of histamine in different body tissues (Konttinen et al, 2013; Panula et al, 2015). The local level of histamine and the differential expression of its receptors are considered important factors in determining the biological response (Panula et al, 2015; Salem, Rozov, et al, 2017) This is important in terms of the recent identification of non-professional histamine-producing cells and their role in mediating crucial pathophysiological processes (Konttinen et al, 2013). Identification Gene cloning Amino acids G-protein coupling HA affinity (pKi) HA activation
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