Pilot Project #2

试点项目

基本信息

批准号：
8849781
负责人：
Selvarangan Ponnazhagan
金额：
$ 4.48万
依托单位：
UNIVERSITY OF ALABAMA AT BIRMINGHAM
依托单位国家：
美国
项目类别：
财政年份：
2014
资助国家：
美国
起止时间：
2014-09-23 至 2018-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8849781
关键词：
Address Adenocarcinoma Adoptive Immunotherapy Alabama Animal Model Autoimmunity CD4 Positive T Lymphocytes CD8B1 gene Cancer Vaccines Cell Line Cell Proliferation Cells Cessation of life Collaborations Communities Comprehensive Cancer Center Development Frequencies Future Goals Growth Factor Human Immune response Immunosuppressive Agents Malignant Neoplasms Malignant neoplasm of prostate Manuscripts Measures Mediating Mentors Mentorship Minority-Serving Institution Mouse Cell Line Mus Natural Killer Cells Organ Outcome PC3 cell line Pilot Projects Production Prostate Prostatic Neoplasms Regulatory T-Lymphocyte Research Research Personnel Research Training Role Second Primary Cancers T-Lymphocyte Training and Education Transforming Growth Factor beta Transforming Growth Factors Transgenic Mice Transgenic Organisms Tumorigenicity United States Universities University of Alabama at Birmingham Cancer Center Vision Work anticancer research base blocking factor cancer diagnosis cancer health disparity cancer initiation career career development design experience immune function men neoplastic cell prostate cancer cell racial and ethnic response transcription factor translational study tumor tumor microenvironment tumor progression

项目摘要

Project Summary: Prostate cancer (PCa) is the most common non-skin malignancy and the cancer second most responsible for death in men in United States. Prior studies with animal models of PCa and with humans demonstrated that the prostate produces various growth factors. Addition or blocking of these factors alters PCa cell proliferation and other functions. Among these factors, transforming growth factor-β1 (TGF-β) is involved in tumorigenicity, displays potent immunosuppressive activities, and is required for the conversion of conventional CD4+ T cells to FoxP3+ regulatory T (TR) cells. TR cells that express the transcription factor Foxp3 are essential for normal immune function; absence of TR cells results in multi-organ autoimmunity and death. A clear role of TGF-β and its effect on TR during PCa development and progression lacks experimental evidence. In this proposal, we plan to investigate the underlying mechanisms involved in the context of TGF-β and/or TR using PCa cell lines, derived from transgenic mouse for prostate cancer (TRAMP), in C57/B6 mice. Of these cell lines, TRAMP- C1 and TRAMP-C2 form tumors; TRAMP-C3 fails to do so. These mouse cell lines of PCa can be used to obtain the long-term goal of this project, which is to address the fundamental question: Do TR cells and/or TGF-β levels relate to differences in tumorigenicity of the TRAMP cell lines (C1, C2, and C3)? The objective of this project is to define the role of TGF-β production by host cells in response to or TGF-β expression by TRAMP cell lines and to establish the function of TGF-β on the conversion of naive CD4+ T cells into Foxp3-expressing TR cells.

项目摘要：前列腺癌（PCA）是最常见的非皮肤恶性肿瘤，第二个癌症是第二个癌症负责美国男性死亡。先前对PCA动物模型和人类的动物模型的研究证明前列腺产生各种生长因素。这些因素的添加或阻塞改变了PCA单元增殖和其他功能。在这些因素中，转化生长因子-β1（TGF-β）参与肿瘤性，显示有效的免疫抑制活性，是常规CD4+的转化所必需的 T细胞到FOXP3+调节性T（TR）细胞。表达转录因子FOXP3的TR细胞对于正常至关重要免疫功能；缺乏TR细胞会导致多器官自身免疫和死亡。 TGF-β及其的明确作用对PCA发育和进展过程中TR的影响缺乏实验证据。在此提案中，我们计划研究使用TGF-β和/或使用TR的潜在机制 PCA细胞系，源自C57/B6小鼠的转基因小鼠前列腺癌（Tramp）。在这些细胞系中流浪汉C1和流浪汉-C2形成肿瘤；流浪汉C3无法做到。这些PCA的鼠标细胞系可用于获得该项目的长期目标，即解决基本问题：TR细胞和/或TGF-β是否水平与流浪性细胞系（C1，C2和C3）的致瘤性差异有关？这个项目的目的是定义宿主细胞对TGF-β产生的作用，响应于流浪细胞系和TO的TGF-β表达或TGF-β表达建立TGF-β对幼稚CD4+ T细胞转化为表达FoxP3的TR细胞的功能。