Study of Progenitor Regulation in Mouse Mammary Gland

小鼠乳腺祖细胞调控研究

• 批准号: 7493960
• 负责人: David J Beebe
• 金额: $ 15.09万
• 依托单位: UNIVERSITY OF WISCONSIN-MADISON
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-09-23 至 2009-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7493960
• 关键词: ATP-Binding Cassette Transporters; Address; Adhesions; Area; Behavior; Biological; Biological Sciences; Biology; Biomedical Research; Bromodeoxyuridine; Cancer Research Project; Cell Communication; Cell Culture Techniques; Cells; Cellular biology; Characteristics; Condition; Cultured Cells; Development; Development Plans; Developmental Biology; Ductal; Effector Cell; Embryonic Development; Engineering; Epithelial Cells; Foundations; Goals; Growth; Hand; Hematopoietic stem cells; Hydrogels; Hyperplasia; In Vitro; Knowledge; Laboratories; Lead; Learning; Life; Malignant Neoplasms; Mammary gland; McArdle Laboratory for Cancer Research; Methods; Modeling; Modification; Morphology; Mus; Natural regeneration; Numbers; Oncogenic; Pathway interactions; Pattern; Physical environment; Placement; Positioning Attribute; Regulation; Research; Staging; Stem cells; Suspension substance; Suspensions; System; Technology; Testing; Training; Tumor Biology; anticancer research; career; cell growth; cell type; design; improved; in vivo; interest; malignant breast neoplasm; mammary epithelium; multidisciplinary; oncology; progenitor; relating to nervous system; research study; response; sensor; skills; stem

DESCRIPTION (provided by applicant): The proposed training in developmental biology and oncology will provide Prof. Beebe with a foundation of biological knowledge and skills (immediate goal) allowing him to develop a comprehensive multidisciplinary cancer research program that fully leverages the cellular/technology interface to explore basic questions pertinent to understanding the biology of tumor development (long term goal). The career development plan integrates didactic training, laboratory skills, and hands-on research under the guidance of Prof. Caroline Alexander of the McArdle Laboratory for Cancer Research. The research is aimed at understanding the regulation of the progenitor fraction in the mammary gland. Recently a description of mammary cells with progenitor characteristics (including BrDu retention, expression of ABC transporter, and morphology/position) has emerged. Unlike the majority of mammary epithelial cells, these long-lived progenitors can be propagated in suspension (mammospheres) and differentiate into both mammary lineages with the provision of appropriate stiumuli. Dr. Alexander's lab has found that in response to the Wnt oncogenic pathway, the progenitor fraction in mouse mammary gland is dysregulated, and this is accompanied by the development of preneoplastic hyperplasia in vivo. In the proposed research, Dr. Beebe will use the information derived from the study of neural and hematopoietic progenitor cells, to test whether the progenitor fraction in the mammary gland is normally actively regulated by factors secreted by cells at other stages of maturation. This hypothesis is not easy to address using traditional culture models. In order to test for growth-regulating cell interactions, progenitor cells (from mammospheres) will be mixed with differentiated cells. Micro scale engineering facilitates studies examining the importance of soluble effectors (no cell contact) as well as cell-associated effectors (cells in contact). The results of such studies will show whether the progenitor compartment is subject to growth regulation by other cell types in the mammary epithelium leading to a more complete understanding of the mechanisms of cancer development in the mammary gland. It is also possible that an improved understanding combined with new culture constructs will lead to a culture model that can support mannary ductal morphagenesis. Such a model would have a significant impact on breast cancer research.

描述（由申请人提供）：拟议的发育生物学和肿瘤学培训将为Beebe教授提供生物学知识和技能的基础（近期目标），使他能够开发一个全面的多学科癌症研究计划，充分利用细胞/技术界面，探索与理解肿瘤发展生物学相关的基本问题（长期目标）。职业发展计划在McArdle癌症研究实验室的Caroline亚历山大教授的指导下整合了教学培训，实验室技能和实践研究。该研究旨在了解乳腺中祖细胞组分的调节。最近出现了具有祖细胞特征（包括BrDu保留、ABC转运蛋白表达和形态/位置）的乳腺细胞的描述。与大多数乳腺上皮细胞不同，这些长寿的祖细胞可以在悬浮液（乳腺球）中繁殖，并在提供适当刺激的情况下分化成两种乳腺谱系。亚历山大博士的实验室发现，在对Wnt致癌通路的反应中，小鼠乳腺中的祖细胞部分失调，并且这伴随着体内肿瘤前增生的发展。在拟议的研究中，Beebe博士将使用来自神经和造血祖细胞研究的信息，来测试乳腺中的祖细胞部分是否通常受到其他成熟阶段细胞分泌的因子的积极调节。这种假设不容易用传统文化模型来解决。为了测试生长调节细胞的相互作用，将祖细胞（来自乳腺球）与分化的细胞混合。微尺度工程有助于研究可溶性效应物（无细胞接触）以及细胞相关效应物（接触细胞）的重要性。这些研究的结果将显示祖细胞隔室是否受到乳腺上皮中其他细胞类型的生长调节，从而更全面地了解乳腺癌发展的机制。 这也是可能的，一个更好的理解与新的文化建设相结合，将导致一个文化模式，可以支持乳腺导管形态发生。 这种模型将对乳腺癌研究产生重大影响。

项目成果

Biological implications of polydimethylsiloxane-based microfluidic cell culture.

• DOI: 10.1039/b903043c
• 发表时间: 2009-08-07
• 期刊: Lab on a chip
• 影响因子: 6.1
• 作者: Regehr KJ;Domenech M;Koepsel JT;Carver KC;Ellison-Zelski SJ;Murphy WL;Schuler LA;Alarid ET;Beebe DJ
• 通讯作者: Beebe DJ

Microfluidic 3D models of cancer.

• DOI: 10.1016/j.addr.2014.07.002
• 发表时间: 2014-12-15
• 期刊: ADVANCED DRUG DELIVERY REVIEWS
• 影响因子: 16.1
• 作者: Sung, Kyung Eun;Beebe, David J.
• 通讯作者: Beebe, David J.

From the cellular perspective: exploring differences in the cellular baseline in macroscale and microfluidic cultures.

• DOI: 10.1039/b814565b
• 发表时间: 2009-02
• 期刊: Integrative biology : quantitative biosciences from nano to macro
• 作者: Paguirigan AL;Beebe DJ
• 通讯作者: Beebe DJ

Microfluidics meet cell biology: bridging the gap by validation and application of microscale techniques for cell biological assays.

• DOI: 10.1002/bies.20804
• 发表时间: 2008-09
• 期刊: BIOESSAYS
• 影响因子: 4
• 作者: Paguirigan, Amy L.;Beebe, David J.
• 通讯作者: Beebe, David J.

An accessible micro-capillary electrophoresis device using surface-tension-driven flow.

一种使用表面张力驱动流动的易于使用的微毛细管电泳装置。

• DOI: 10.1002/elps.200800595
• 发表时间: 2009
• 期刊: Electrophoresis
• 影响因子: 2.9
• 作者: Mohanty,SwomitraK;Warrick,Jay;Gorski,Jack;Beebe,DavidJ
• 通讯作者: Beebe,DavidJ