{"title":"鳞状细胞和内皮细胞之间的配体-受体相互作用诱导头颈部鳞状细胞癌。","authors":"Takahiro Ishiyama, Daisuke Sano, Hideaki Takahashi, Nobuhiko Oridate, Yutaka Suzuki, Satoshi Fujii","doi":"10.1111/cas.70085","DOIUrl":null,"url":null,"abstract":"<p><p>Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC). We investigated ligand-receptor interactions between squamous epithelial and endothelial cells of IPCLs using Visium analysis on frozen, formalin-fixed and paraffin-embedded (FFPE) tissues from hypopharyngeal squamous epithelial lesions. We examined the protein expression in hypopharyngeal superficial squamous epithelial lesions using immunohistochemistry and immunofluorescence. mRNA expression levels of these genes in SCC and non-tumor tissues were analyzed using RT-qPCR. Phenotypic changes were analyzed by inducing candidate genes into SCC cell lines via a lentivirus system. Visium analysis revealed that Fibronectin 1 (FN1) acted as a ligand in endothelial cells, Cellular communication network factor 1 (CCN1) as a ligand in SCC cells, and Integrin subunit alpha V (ITGAV) as a receptor for both FN1 and CCN1. The expression of these three candidates increased in low-grade dysplasia, an early stage of neoplastic lesions, and was significantly higher in invasive SCCs, except for CCN1. When ITGAV was introduced into SCC cell lines (FaDu and Detroit 562) and HaCaT cells treated with FN1, the cells showed increased proliferation ability. SCC develops via ligand-receptor molecular interactions between squamous epithelial and vascular endothelial cells in IPCLs.</p>","PeriodicalId":48943,"journal":{"name":"Cancer Science","volume":" ","pages":""},"PeriodicalIF":5.7000,"publicationDate":"2025-05-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Ligand-Receptor Interactions Between Squamous and Endothelial Cells Induce Head and Neck Squamous Cell Carcinoma.\",\"authors\":\"Takahiro Ishiyama, Daisuke Sano, Hideaki Takahashi, Nobuhiko Oridate, Yutaka Suzuki, Satoshi Fujii\",\"doi\":\"10.1111/cas.70085\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC). We investigated ligand-receptor interactions between squamous epithelial and endothelial cells of IPCLs using Visium analysis on frozen, formalin-fixed and paraffin-embedded (FFPE) tissues from hypopharyngeal squamous epithelial lesions. We examined the protein expression in hypopharyngeal superficial squamous epithelial lesions using immunohistochemistry and immunofluorescence. mRNA expression levels of these genes in SCC and non-tumor tissues were analyzed using RT-qPCR. Phenotypic changes were analyzed by inducing candidate genes into SCC cell lines via a lentivirus system. Visium analysis revealed that Fibronectin 1 (FN1) acted as a ligand in endothelial cells, Cellular communication network factor 1 (CCN1) as a ligand in SCC cells, and Integrin subunit alpha V (ITGAV) as a receptor for both FN1 and CCN1. The expression of these three candidates increased in low-grade dysplasia, an early stage of neoplastic lesions, and was significantly higher in invasive SCCs, except for CCN1. When ITGAV was introduced into SCC cell lines (FaDu and Detroit 562) and HaCaT cells treated with FN1, the cells showed increased proliferation ability. SCC develops via ligand-receptor molecular interactions between squamous epithelial and vascular endothelial cells in IPCLs.</p>\",\"PeriodicalId\":48943,\"journal\":{\"name\":\"Cancer Science\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":5.7000,\"publicationDate\":\"2025-05-26\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cancer Science\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1111/cas.70085\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cancer Science","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1111/cas.70085","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
引用次数: 0
摘要
窄带成像(NBI)的进展显示,头颈部鳞状上皮病变的形成伴随着鳞状上皮细胞和乳头内毛细血管袢(IPCLs)的变化。然而,鳞状上皮细胞和内皮细胞(ECs)之间促进IPCL增殖的分子相互作用尚不清楚。本研究旨在探讨头颈部鳞状细胞癌(SCC)形成过程中实质鳞状细胞与间质ipcl之间的合作机制。我们对下咽鳞状上皮病变的冷冻、福尔马林固定和石蜡包埋(FFPE)组织进行了Visium分析,研究了IPCLs鳞状上皮和内皮细胞之间的配体-受体相互作用。我们用免疫组织化学和免疫荧光检测了下咽浅表鳞状上皮病变中的蛋白表达。采用RT-qPCR分析这些基因在SCC和非肿瘤组织中的mRNA表达水平。通过慢病毒系统诱导候选基因进入SCC细胞系,分析表型变化。Visium分析显示,内皮细胞中纤维连接蛋白1 (FN1)作为配体,SCC细胞中细胞通讯网络因子1 (CCN1)作为配体,整合素亚单位α V (ITGAV)作为FN1和CCN1的受体。除CCN1外,这三种候选基因的表达在低级别非典型增生(早期肿瘤病变)中增加,在侵袭性SCCs中显著增加。将ITGAV引入SCC细胞系(FaDu和Detroit 562)和经FN1处理的HaCaT细胞,细胞的增殖能力增强。鳞状细胞癌是通过鳞状上皮细胞和血管内皮细胞之间的配体-受体分子相互作用而发生的。
Ligand-Receptor Interactions Between Squamous and Endothelial Cells Induce Head and Neck Squamous Cell Carcinoma.
Advances in narrowband imaging (NBI) have revealed that squamous epithelial lesions form alongside changes in squamous epithelial cells and intrapapillary capillary loops (IPCLs) in the head and neck. However, the molecular interactions between squamous epithelial cells and endothelial cells (ECs) that promote IPCL proliferation are unclear. This study aimed to identify the mechanisms of cooperation between parenchymal squamous cells and stromal IPCLs during the formation of head and neck squamous cell carcinoma (SCC). We investigated ligand-receptor interactions between squamous epithelial and endothelial cells of IPCLs using Visium analysis on frozen, formalin-fixed and paraffin-embedded (FFPE) tissues from hypopharyngeal squamous epithelial lesions. We examined the protein expression in hypopharyngeal superficial squamous epithelial lesions using immunohistochemistry and immunofluorescence. mRNA expression levels of these genes in SCC and non-tumor tissues were analyzed using RT-qPCR. Phenotypic changes were analyzed by inducing candidate genes into SCC cell lines via a lentivirus system. Visium analysis revealed that Fibronectin 1 (FN1) acted as a ligand in endothelial cells, Cellular communication network factor 1 (CCN1) as a ligand in SCC cells, and Integrin subunit alpha V (ITGAV) as a receptor for both FN1 and CCN1. The expression of these three candidates increased in low-grade dysplasia, an early stage of neoplastic lesions, and was significantly higher in invasive SCCs, except for CCN1. When ITGAV was introduced into SCC cell lines (FaDu and Detroit 562) and HaCaT cells treated with FN1, the cells showed increased proliferation ability. SCC develops via ligand-receptor molecular interactions between squamous epithelial and vascular endothelial cells in IPCLs.
期刊介绍:
Cancer Science (formerly Japanese Journal of Cancer Research) is a monthly publication of the Japanese Cancer Association. First published in 1907, the Journal continues to publish original articles, editorials, and letters to the editor, describing original research in the fields of basic, translational and clinical cancer research. The Journal also accepts reports and case reports.
Cancer Science aims to present highly significant and timely findings that have a significant clinical impact on oncologists or that may alter the disease concept of a tumor. The Journal will not publish case reports that describe a rare tumor or condition without new findings to be added to previous reports; combination of different tumors without new suggestive findings for oncological research; remarkable effect of already known treatments without suggestive data to explain the exceptional result. Review articles may also be published.