Role of Cancer Stem Cells in Malignant Progression of Ductal Carcinoma in Situ.

癌症干细胞在原位导管癌恶性进展中的作用。

• 批准号: 7250765
• 负责人: FARIBA BEHBOD
• 金额: $ 13.61万
• 依托单位: BAYLOR COLLEGE OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-01 至 2009-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7250765
• 关键词: Accounting; Address; American; Basic Science; Biological; Biological Assay; Brain Neoplasms; Breast; Cancer Biology; Cancer Center; Cancerous; Cell Adhesion Molecules; Cell Line; Cell Separation; Cell surface; Cells; Cellular biology; Clinical; Coculture Techniques; Collaborations; Commit; Data; Development; Diagnosis; Differentiation and Growth; Dilution Techniques; Disease; Distant Metastasis; Doctor of Philosophy; Education; Endothelial Cells; Environment; Epithelial; Epithelial Cells; Exhibits; Fatty acid glycerol esters; Focus Groups; Frequencies; Generations; Genes; Genetic; Goals; Growth; Hematopoietic stem cells; Heterogeneity; Housing; Human; Immunocompromised Host; In Vitro; Invasive; Invasive Lesion; K-Series Research Career Programs; Label; Lead; Lesion; Life; Malignant - descriptor; Malignant Neoplasms; Mammary Neoplasms; Mammary gland; Mediating; Medicine; Modeling; Molecular; Molecular Target; Mus; Noninfiltrating Intraductal Carcinoma; Normal tissue morphology; Palpable; Patients; Phenotype; Population; Premalignant; Premalignant Cell; Prevention; Property; Rate; Recurrence; Research; Research Design; Research Personnel; Risk Assessment; Role; Sampling; Signal Transduction; Standards of Weights and Measures; Stem cells; Surface; Techniques; Testing; Therapeutic; Time; Translational Research; Transplantation; Tumorigenicity; Woman; Xenograft procedure; base; cancer cell; cancer stem cell; career; college; disorder later incidence prevention; experience; improved; in vivo; leukemia; malignant breast neoplasm; matrigel; mortality; mouse model; novel; novel strategies; post-doctoral training; prevent; progenitor; prognostic; programs; relating to nervous system; self-renewal; stem; tumor

DESCRIPTION (provided by applicant): My specific aims are to examine the role of cancer stem cells and their niche microenvironment in malignant progression of subtypes of human breast premalignancy, ductal carcinoma in situ (DCIS). The objectives are to test whether premalignant cell lines, SUM225, MCF10ATDCIS.com, and subtypes of human DCIS contain distinct cancer stem cell subpopulations which exhibit unique cancer stem cell properties of increased self-renewal potential, quiescence, and tumorigenicity. My strategy is to use fluorescent activated cell sorting (FACS) and known surface markers to isolate stem/progenitor and differentiated subpopulations and to examine their cancer stem cell properties which include, 1) in vitro self-renewal and differentiation potential by standard mammosphere assay and colony formation in Matrigel, respectively, 2) in vivo long term and short term self-renewal by using a novel strategy of xenotransplantation into humanized stroma of mice fat pads, 3) tumorigenicity by growth rate and potential to form invasive lesions, and 4) quiescence by long term label retaining studies. Furthermore, the role of endothelial cells in establishing a cancer stem cell niche microenvironment will be examined by in vitro co-culture and in vivo co-transplantation studies. My rationale is that cancer stem cells and normal tissue stem cells express similar surface markers by which they may be identified and characterized. Once cancer stem cells are identified, efforts will be aimed at defining their unique gene profiles. These studies will provide a basis for discovery of molecular targets for risk assessment, prevention of recurrence, and malignant progression tailored to subtypes of DCIS. My long term career goal is to lead a research group focused towards prevention of human breast cancer malignant progression in a translational research environment. I served as an academic and clinical pharmacologist for seven years before obtaining a Ph.D. and post-doctoral training in basic sciences in cellular signaling and mouse mammary gland stem cell biology. The Career Development Award is an excellent opportunity to gain additional experience in research in human breast cancer in collaboration with the Breast Cancer Center at Baylor College of Medicine. Baylor College of Medicine houses exceptional research centers and facilities and provides an ample opportunity for scientific collaboration, and education. Relevance: Breast pre-cancer lesions may contain a rare population of cancer stem cells. Cancer stem cells may be unique to different types of pre-cancer lesions and may explain why some patients will experience recurrences or develop invasive cancers while others do not. My goal is to examine the role of cancer stem cells in invasive progression of subtypes of pre-cancer lesions and to develop individualized strategies for risk assessment and prevention of invasive breast cancer.

描述（由申请人提供）：我的具体目的是检查癌症干细胞及其小众微环境在人类乳腺癌，导管癌的亚型恶性进展中的作用，原位（DCIS）。这些目的是测试预启示性细胞系SUM225，MCF10ATDCIS.com和人类DCIS的亚型是否包含独特的癌症干细胞亚群，这些癌细胞亚群显示出独特的癌症干细胞性质，具有增加自我更新潜力，静态和肿瘤性的性质。我的策略是使用荧光活化的细胞分选（FACS）和已知的表面标记来分离茎/祖细胞和分化的亚群，并检查其癌症干细胞的特性，其中包括，1）通过标准的哺乳动物分析和成群的体外自我更新和分化潜力，分别使用Matrigel中的Matrigel In In Vivo Self-Rynal Aniral Aniral An Niffal-Ar-ReNEL AR-RENER AR-RENER AR-RENERINE，2）小鼠的基质脂肪垫，3）按生长速率和形成侵入性病变的潜力以及长期标记保留研究的静止。此外，将通过体外共培养和体内共移植研究来检查内皮细胞在建立癌症干细胞小众微环境中的作用。我的理由是，癌症干细胞和正常组织干细胞表达了相似的表面标记，可以通过这些标记来识别和表征它们。一旦确定了癌症干细胞，将旨在定义其独特的基因谱。这些研究将为发现分子靶标的风险评估，预防复发性和针对DCIS亚型量身定制的恶性进展提供基础。 我的长期职业目标是领导一个专注于预防人类乳腺癌恶性肿瘤进展的研究小组。在获得博士学位之前，我曾担任学术和临床药物学家七年。细胞信号传导和小鼠乳腺干细胞生物学中基本科学的博士后训练。职业发展奖是一个与贝勒医学院乳腺癌中心合作获得人类乳腺癌研究经验的绝佳机会。贝勒医学院拥有卓越的研究中心和设施，并为科学合作和教育提供了充足的机会。 相关性：乳腺癌病变可能含有罕见的癌症干细胞。癌症干细胞可能是不同类型的前癌病变独有的，并且可以解释为什么有些患者会经历复发或发展侵入性癌症而其他患者却没有。我的目标是检查癌症干细胞在前癌病变亚型的侵入性进展中的作用，并制定个性化的策略，以评估和预防侵入性乳腺癌。