Stem-like Cancer Cells in Breast Tumorigenesis

乳腺肿瘤发生中的干细胞样癌细胞

• 批准号: 7387336
• 负责人: ROBERT Y TSAI
• 金额: $ 24.52万
• 依托单位: TEXAS A&M UNIVERSITY HEALTH SCIENCE CTR
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7387336
• 关键词: Ablation; Address; Animals; Breast; Breast Cancer Cell; Breast Cancer Treatment; Breast Carcinoma; Cancer cell line; Cell physiology; Cells; Color; Development; Drug resistance; Epithelial Cells; Estradiol; Estrogens; Flow Cytometry; Frequencies; Gene Expression Profile; Genetic; Goals; Growth; Guanosine Triphosphate Phosphohydrolases; Health; Human; In Vitro; Life; Malignant - descriptor; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Mammary gland; Medical center; Modeling; Molecular; Molecular Target; Mus; Nature; Neoplasm Metastasis; Outcome; Partner in relationship; Pathogenesis; Pattern; Personal Satisfaction; Pharmaceutical Preparations; Phenotype; Positioning Attribute; Property; Proteins; Range; Rate; Reagent; Recurrence; Research; Research Personnel; Resistance; Role; Stem Cell Research; Stem cells; Surface; System; Testing; Texas; Therapeutic; Training; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Tumor Stem Cells; Tumor Tissue; Work; anticancer research; base; cancer cell; cancer stem cell; cancer therapy; cell type; design; embryonic stem cell; gene therapy; in vivo; innovation; insight; malignant breast neoplasm; mouse model; neoplastic cell; nerve stem cell; novel; programs; rapid growth; response; self-renewal; stem; tumor; tumor initiation; tumor progression; tumorigenesis

DESCRIPTION (provided by applicant): The long-range goal of my research is to uncover the nature of the cancer stem cells, and to design therapeutic approaches that can specifically target these cells for the treatment of breast cancers. The objective of this application is to establish the expression pattern of NS and Ngp1 in breast cancer cells, determine the growth phenotype and gene expression profile of NS- and Ngp1-expressing cells, and provide experimental evidence that demonstrates the role of NS+ cells in breast tumorigenesis. The central hypothesis is that NS and Ngp1 are preferentially expressed by the stem-like cells in breast tumors, and that these cells are responsible for the rapid growth, drug resistance, and high metastasis of malignant breast cancers. The rationale is that cancer stem cells, which are responsible for the high growth rate and drug resistance of malignant breast cancers, share common molecules such as NS and Ngp1 with somatic stem cells to drive the self-renewing machinery. Therefore, eliminating NS-expressing breast cancer cells will inhibit tumor initiation and progression. To accomplish the overall objective of this proposal, three specific aims will be pursued. The first aim is to establish the expression pattern of NS and Ngp1 in normal breast tissues and breast cancer cells. The second aim is to determine the cellular and molecular properties of those NS- and Ngp1-expressing cells by genetically marking these cells with living color proteins and purifying them by flow cytometry. The third aim is to determine the role of NS+ cells in the development, progression, and recurrence of breast tumors by evaluating the consequences of their elimination. An inducible cell ablation system will be employed to target the NS+ cells in transgenic animals. These results will provide the much-needed justification for the use of stem cell-targeting therapy in cancer treatment, and valuable information for developing new pharmacological and genetic therapies that can specifically target these cancer stem cells in order to cure advanced breast carcinomas.

描述（由申请人提供）：我研究的长期目标是揭示癌症干细胞的性质，并设计可以特异性靶向这些细胞治疗乳腺癌的治疗方法。 本申请的目的是建立NS和Ngp 1在乳腺癌细胞中的表达模式，确定NS-和Ngp 1表达细胞的生长表型和基因表达谱，并提供证明NS+细胞在乳腺肿瘤发生中的作用的实验证据。 核心假设是NS和Ngp 1优先由乳腺肿瘤中的干细胞样细胞表达，并且这些细胞负责恶性乳腺癌的快速生长、耐药性和高转移。 其基本原理是，癌症干细胞是恶性乳腺癌的高生长率和耐药性的原因，它们与体干细胞共享共同的分子，如NS和Ngp 1，以驱动自我更新机制。 因此，消除表达NS的乳腺癌细胞将抑制肿瘤的发生和进展。 为实现本建议的总体目标，将追求三个具体目标。 第一个目的是建立NS和Ngp 1在正常乳腺组织和乳腺癌细胞中的表达模式。 第二个目的是确定这些NS-和Ngp 1-表达细胞的细胞和分子特性的遗传标记这些细胞与活的颜色蛋白和纯化它们通过流式细胞术。 第三个目的是通过评估NS+细胞消除的后果来确定NS+细胞在乳腺肿瘤的发展、进展和复发中的作用。 将采用诱导型细胞消融系统来靶向转基因动物中的NS+细胞。 这些结果将为在癌症治疗中使用干细胞靶向治疗提供急需的理由，并为开发新的药理学和遗传疗法提供有价值的信息，这些疗法可以特异性靶向这些癌症干细胞，以治愈晚期乳腺癌。