Interleukin-33 in skin carcinogenesis

Interleukin-33 在皮肤癌发生中的作用

• 批准号: 8638636
• 负责人: TRACI A WILGUS
• 金额: $ 23.06万
• 依托单位: OHIO STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-12-01 至 2015-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8638636
• 关键词: Acute; Animals; Basal cell carcinoma; Case Study; Cause of Death; Cells; Cessation of life; Chronic; Cicatrix; Clinical; Cutaneous; DNA Damage; Data; Development; Disease; Distant; Epithelial; Excision; Exposure to; General Population; Growth and Development function; HIV; Health Care Costs; High Prevalence; Human; Inflammation; Inflammation Mediators; Inflammatory; Inflammatory Response; Interleukins; Intervention; Knockout Mice; Lead; Lesion; Malignant Neoplasms; Mediator of activation protein; Modeling; Morbidity - disease rate; Mus; Mutation; Neoplasm Metastasis; Operative Surgical Procedures; Organ; Organ Transplantation; Patients; Population; Process; Publishing; Risk; Risk Factors; Role; Skin; Skin Cancer; Skin Carcinogenesis; Skin Carcinoma; Skin Neoplasms; Solid; Squamous cell carcinoma; Staging; Surface; Testing; The Sun; Time; Transplant Recipients; Ultraviolet Rays; Up-Regulation; base; cancer diagnosis; cancer type; clinically significant; cytokine; effective therapy; immunosuppressed; information gathering; keratinocyte; mast cell; mortality; neoplastic cell; neutrophil; new therapeutic target; prevent; public health relevance; receptor; research study; skin squamous cell carcinoma; treatment strategy; tumor; tumor microenvironment

PROJECT SUMMARY: Non-melanoma skin cancers (NMSC), which include basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), are the most commonly diagnosed cancers with over a million new cases annually in the US. Of the main NMSC subtypes, SCC has a greater risk for metastasis and mortality. While the mortality rate is not as high for SCC compared to some other cancer types, there are very few effective non-surgical interventions. As a result, SCC can lead to significant morbidity and financial burden for patients. One of the most important risk factors for SCC development is ultraviolet light (UV) exposure from the sun. UV damages the DNA, leading to mutations in epithelial keratinocytes on the surface of the skin and consequently, to the formation of tumors. Additionally, UV exposure induces a robust cutaneous inflammatory response, and inflammation has been shown by our group as well as others to drive skin carcinogenesis. Recently, the function of the relatively newly described cytokine, IL-33, has started to be described in the skin. Several studies in addition to preliminary data included in this application have shown that IL-33 stimulates inflammation in the skin. Furthermore, recently published data and our preliminary results show that IL-33 expression is upregulated in keratinocytes after UV exposure during times of peak inflammation. Our preliminary data also show that IL-33 is expressed by tumor cells in both murine and human skin tumors. Thus far, there is very little information about the role of IL-33 in any cancer type, including the skin; however, based on its upregulation by UV and its demonstrated role in cutaneous inflammation, IL-33 is likely to be a key mediator of skin carcinogenesis. The central hypothesis of the proposed studies is that IL-33 promotes skin carcinogenesis by altering UV- induced inflammation. The following Specific Aims will be carried out to test this hypothesis: Aim 1 - Examine the function of IL-33 in UV-induced inflammation; Aim 2 - Determine the importance of IL-33 in UV-induced skin carcinogenesis. Overall, these experiments will generate valuable new information about IL-33 in the development and growth of SCC and will be the first steps in determining whether it is logical to develop treatment strategies aimed at blocking the effects of IL-33. .

项目概要： 非黑色素瘤皮肤癌 (NMSC)，包括基底细胞癌 (BCC) 和鳞状细胞癌 癌 (SCC) 是最常诊断的癌症，每年新增病例超过一百万例 我们。在主要的 NMSC 亚型中，鳞状细胞癌具有更高的转移和死亡风险。虽然死亡率 与其他一些癌症类型相比，鳞状细胞癌的发病率并不高，有效的非手术治疗方法非常少 干预措施。因此，鳞状细胞癌可能会给患者带来严重的发病率和经济负担。 SCC 发展最重要的风险因素之一是来自太阳的紫外线 (UV) 照射。 紫外线会损伤 DNA，导致皮肤表面的上皮角质形成细胞发生突变， 从而导致肿瘤的形成。此外，紫外线照射会诱发严重的皮肤炎症 我们的小组以及其他人已经证明炎症会导致皮肤癌的发生。 最近，人们开始描述相对较新的细胞因子 IL-33 在皮肤中的功能。 除本申请中包含的初步数据外，多项研究表明 IL-33 可以刺激 皮肤发炎。此外，最近发表的数据和我们的初步结果表明 IL-33 在炎症高峰期暴露于紫外线后，角质形成细胞中的表达上调。我们的 初步数据还表明，小鼠和人类皮肤肿瘤中的肿瘤细胞都表达 IL-33。因此 到目前为止，关于 IL-33 在任何癌症类型（包括皮肤癌）中的作用的信息还很少；然而，基于 紫外线对其上调及其在皮肤炎症中的作用，IL-33 可能是一个关键因素 皮肤癌发生的介质。 该研究的中心假设是 IL-33 通过改变 UV-33 来促进皮肤癌的发生。 诱发炎症。将执行以下具体目标来检验该假设： 目标 1 - 检查 IL-33 在紫外线诱导的炎症中的功能；目标 2 - 确定 IL-33 在紫外线诱导中的重要性 皮肤癌发生。总体而言，这些实验将产生有关 IL-33 的有价值的新信息 SCC 的发展和成长，将是确定发展是否合乎逻辑的第一步 旨在阻断 IL-33 作用的治疗策略。 。