Investigating Breast Cancer Collective Invasion

调查乳腺癌集体侵袭

基本信息

批准号：
8230595
负责人：
Gray W Pearson
金额：
$ 32.94万
依托单位：
UT SOUTHWESTERN MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2011
资助国家：
美国
起止时间：
2011-03-01 至 2016-02-28
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/8230595
关键词：
Address Animal Model Architecture Basement membrane Biological Breast Cancer Cell Breast Carcinoma Cancer Patient Cell Line Cells Cessation of life Characteristics Conditioned Culture Media Connective Tissue Cytoskeleton Development Distant Distant Metastasis Duct (organ) structure Epithelium Event Fibroblasts Goals Growth Human Image In Situ Lesion Individual Invaded Lesion Life Lobule Malignant Epithelial Cell Mammary Ductal Carcinoma Mammary Neoplasms Mammary gland MicroRNAs Modeling Molecular Neoplasm Metastasis Noninfiltrating Intraductal Carcinoma Paracrine Communication Pathology Patients Population Resolution Risk Role Sampling Signal Pathway Site Staging Stromal Cells System Therapeutic Intervention Time Tumor Cell Invasion Tumor Pathology Xenograft Model cancer cell cell behavior cell motility cellular imaging clinically significant epithelial to mesenchymal transition genetic regulatory protein in vivo intercalation loss of function malignant breast neoplasm neoplastic neoplastic cell public health relevance transcription factor tumor tumor progression

项目摘要

DESCRIPTION (provided by applicant): During tumor progression the well-ordered architecture of the mammary gland becomes disrupted as hyperproliferative cells accumulate in the luminal space of ducts and lobules. Over time the neoplastic cells can invade into the stroma where they can access the vasculature system and disseminate to distant sites throughout the body. Although the induction of invasive growth is a key step in the metastatic cascade, how breast cancer cells become invasive remains poorly understood. Using an organotypic culture system and animal models we propose to determine (1) how cell motility is regulated by intracellular signaling pathways during collective invasion; (2) how mammary fibroblasts induce collective invasion and (3) how subpopulations of neoplastic cells trigger collective invasion. Deciphering the requirements for breast cancer invasion could identify targets for therapeutic intervention in both the tumor and the microenvironment. PUBLIC HEALTH RELEVANCE: Distant metastases are responsible for nearly all breast cancer patient deaths. A critical step leading to the development of metastases is the invasion of tumor cells into connective tissue. We will investigate how tumor cells become invasive with the goals of more accurately identifying which patients are at risk of developing metastases and identifying targets of therapeutic intervention.

描述（由申请人提供）：在肿瘤进展过程中，随着超增殖细胞积累在管道和小叶的腔空间中，乳腺的有序结构被破坏。随着时间的流逝，肿瘤细胞可以入侵基质，在那里它们可以进入脉管系统并传播到整个体内的远处。尽管诱导侵入性生长是转移性级联反应的关键步骤，但乳腺癌细胞的侵入性如何保持不足。使用器官型培养系统和动物模型，我们建议在集体侵袭过程中确定以下细胞运动如何受细胞内信号通路的调节；（2）乳腺成纤维细胞如何诱导集体入侵，以及（3）肿瘤细胞的亚群如何触发集体侵袭。解密对乳腺癌侵袭的要求可以识别肿瘤和微环境中治疗干预的靶标。公共卫生相关性：远处转移造成几乎所有乳腺癌患者死亡的原因。导致转移发展发展的关键步骤是侵袭肿瘤细胞进入结缔组织。我们将研究肿瘤细胞如何侵入性，以更准确地识别哪些患者有发生转移的风险并确定治疗干预的靶标。