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. .

项目摘要： 非黑色素瘤皮肤癌（NMSC），其中包括基底细胞癌（BCC）和鳞状细胞 癌（SCC）是最常见的癌症，每年有超过一百万个新病例 我们。在主要NMSC亚型中，SCC具有更大的转移和死亡风险。而死亡率 与其他一些癌症类型相比，SCC的高度不高，有效的非手术很少 干预措施。结果，SCC可以导致患者的大量发病率和经济负担。 SCC开发最重要的危险因素之一是紫外线（UV）暴露于太阳。 紫外线会损坏DNA，导致皮肤表面上的上皮角质形成细胞突变 因此，肿瘤的形成。另外，紫外线暴露会诱发强大的皮肤炎症 我们的小组以及其他人都表明了反应和炎症，以驱动皮肤致癌。 最近，相对新描述的细胞因子IL-33的功能已开始在皮肤中描述。 除本应用程序中包括的初步数据外，还表明IL-33刺激了一些研究 皮肤炎症。此外，最近发布的数据，我们的初步结果表明IL-33 在峰值炎症时期，在紫外线暴露后，在角质形成细胞中表达上调。我们的 初步数据还表明，IL-33均由鼠类和人类皮肤肿瘤中的肿瘤细胞表达。因此 到目前为止，关于IL-33在任何癌症类型（包括皮肤）中的作用的信息很少。但是，基于 在紫外线上调及其在皮肤炎症中的作用，IL-33可能是关键 皮肤致癌的介体。 拟议的研究的中心假设是IL-33通过改变紫外线来促进皮肤致癌作用。 诱发炎症。将执行以下具体目标以检验以下假设：目标1-检查 IL-33在紫外线引起的炎症中的功能； AIM 2-确定IL-33在紫外线诱导中的重要性 皮肤致癌。总体而言，这些实验将在有关IL-33的有价值的新信息中。 SCC的发展和成长将是确定发展是否合乎逻辑的第一步 旨在阻止IL-33影响的治疗策略。 。