Abdelhakim Salem1,2, Rabeia Almahmoudi3, Dyah Listyarifah4,3,5, Maria Siponen6,7, Katariina Maaninka8, Ahmed Al-Samadi3, Tuula Salo3,9,10, Kari K Eklund4,11. 1. Department of Clinical Medicine, Clinicum, University of Helsinki, Helsinki, Finland. Abdelhakim.Salem@helsinki.fi. 2. Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Haartmaninkatu 8, Biomedicum Helsinki 1, PO Box 63, FI-00029 HUS, Helsinki, Finland. Abdelhakim.Salem@helsinki.fi. 3. Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Haartmaninkatu 8, Biomedicum Helsinki 1, PO Box 63, FI-00029 HUS, Helsinki, Finland. 4. Department of Clinical Medicine, Clinicum, University of Helsinki, Helsinki, Finland. 5. Department of Dental Biomedical Sciences, Faculty of Dentistry, Universitas Gadjah Mada, Yogyakarta, Indonesia. 6. Department of Oral and Maxillofacial Diseases, Kuopio University Hospital, Kuopio, Finland. 7. Institute of Dentistry, Faculty of Health Sciences, University of Eastern Finland, Joensuu, Finland. 8. Wihuri Research Institute, Biomedicum Helsinki, Helsinki, Finland. 9. Cancer and Translational Medicine Research Unit, University of Oulu, Oulu, Finland. 10. Medical Research Center, Oulu University Hospital, Oulu, Finland. 11. Department of Rheumatology, Helsinki University and Helsinki University Hospital, Helsinki, Finland.
Abstract
PURPOSE: Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess H4R expression in OTSCC patients and in OTSCC-derived cell lines. METHODS: Biopsies taken from OED, OTSCC and healthy oral mucosa were studied by immunostaining. Primary human oral keratinocytes (HOKs) and two OTSCC-derived cell lines (HSC-3 and SCC-25) were used for the in vitro studies. Quantitative real-time PCR was used to measure oncogene expression in the stimulated HOKs. RESULTS: We found that H4R-immunoreactivity was significantly reduced in the OED and OTSCC samples, especially in the samples with higher histopathological grades and noticeably increased mast cell counts. The presence of H4R in HSC-3 cells had clearly waned, in contrast to the HOKs. Gene expression data indicated that histamine-relevant inflammatory and environmental elements may participate in the regulation of oncogenes. CONCLUSIONS: Our results suggest an association between H4R and oral carcinogenesis. Furthermore, our findings raise a potential implication of histamine-mediated factors in the regulation of oncogenes, possibly via mast cells, as crucial components of the tumor microenvironment. The identification of new elements that govern oral cancer development is highly relevant for the development of novel therapeutic approaches in OTSCC.
PURPOSE: Recent reports indicate that histamine and its novel, high-affinity histamine H4 receptor (H4R) play a role in carcinogenesis, and thus H4R signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of H4R in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess H4R expression in OTSCC patients and in OTSCC-derived cell lines. METHODS: Biopsies taken from OED, OTSCC and healthy oral mucosa were studied by immunostaining. Primary human oral keratinocytes (HOKs) and two OTSCC-derived cell lines (HSC-3 and SCC-25) were used for the in vitro studies. Quantitative real-time PCR was used to measure oncogene expression in the stimulated HOKs. RESULTS: We found that H4R-immunoreactivity was significantly reduced in the OED and OTSCC samples, especially in the samples with higher histopathological grades and noticeably increased mast cell counts. The presence of H4R in HSC-3 cells had clearly waned, in contrast to the HOKs. Gene expression data indicated that histamine-relevant inflammatory and environmental elements may participate in the regulation of oncogenes. CONCLUSIONS: Our results suggest an association between H4R and oral carcinogenesis. Furthermore, our findings raise a potential implication of histamine-mediated factors in the regulation of oncogenes, possibly via mast cells, as crucial components of the tumor microenvironment. The identification of new elements that govern oral cancer development is highly relevant for the development of novel therapeutic approaches in OTSCC.
Authors: Rajan S Patel; Jonathan R Clark; Richard Dirven; Rebecca Wyten; Kan Gao; Christopher J O'Brien Journal: ANZ J Surg Date: 2009 Jan-Feb Impact factor: 1.872
Authors: A Salem; S Rozov; A Al-Samadi; V Stegajev; D Listyarifah; V-P Kouri; X Han; D Nordström; J Hagström; K K Eklund Journal: Br J Dermatol Date: 2017-03-22 Impact factor: 9.302
Authors: A Salem; A Al-Samadi; V Stegajev; H Stark; R Häyrinen-Immonen; M Ainola; J Hietanen; Y T Konttinen Journal: Oral Dis Date: 2014-10-08 Impact factor: 3.511