Department of Clinical Medicine, Clinicum, University of Helsinki, Helsinki, Finland.
Department of Oral and Maxillofacial Diseases, Clinicum, University of Helsinki, Haartmaninkatu 8, Biomedicum Helsinki 1, PO Box 63, FI-00029 HUS, Helsinki, Finland.
Cell Oncol (Dordr). 2017 Dec;40(6):621-630. doi: 10.1007/s13402-017-0336-6. Epub 2017 Jun 26.
Recent reports indicate that histamine and its novel, high-affinity histamine H receptor (HR) play a role in carcinogenesis, and thus HR signalling has become a focus of increasing interest in the pathogenesis of many cancers. The roles of HR in oral epithelial dysplasia (OED) and oral tongue squamous cell carcinoma (OTSCC) are unknown. The purpose of this study was to assess HR expression in OTSCC patients and in OTSCC-derived cell lines.
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.
We found that HR-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 HR 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.
Our results suggest an association between HR 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.
最近的报告表明,组胺及其新型高亲和力组胺 H 受体(HR)在肿瘤发生中发挥作用,因此 HR 信号转导已成为许多癌症发病机制中越来越引人关注的焦点。HR 在口腔上皮异型增生(OED)和口腔舌鳞状细胞癌(OTSCC)中的作用尚不清楚。本研究旨在评估 HR 在 OTSCC 患者和 OTSCC 衍生细胞系中的表达。
通过免疫染色研究取自 OED、OTSCC 和健康口腔黏膜的活检。使用原代人口腔角质形成细胞(HOK)和两种 OTSCC 衍生细胞系(HSC-3 和 SCC-25)进行体外研究。使用定量实时 PCR 测量刺激的 HOK 中的癌基因表达。
我们发现 HR 免疫反应性在 OED 和 OTSCC 样本中明显降低,尤其是在具有较高组织病理学分级和明显增加的肥大细胞计数的样本中。与 HOK 相比,HSC-3 细胞中 HR 的存在明显减弱。基因表达数据表明,与组胺相关的炎症和环境因素可能参与了癌基因的调节。
我们的结果表明 HR 与口腔癌发生之间存在关联。此外,我们的研究结果提出了组胺介导的因素通过肥大细胞可能在调节癌基因方面具有潜在意义,肥大细胞是肿瘤微环境的重要组成部分。确定新的元素来控制口腔癌的发展对于开发 OTSCC 的新治疗方法具有重要意义。