Investigating Breast Cancer Collective Invasion

调查乳腺癌集体侵袭

• 批准号: 8026563
• 负责人: Gray W Pearson
• 金额: $ 32.89万
• 依托单位: UT SOUTHWESTERN MEDICAL CENTER
• 依托单位国家: 美国
• 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/8026563
• 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; transcription factor; tumor; tumor progression

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（由申请方提供）：在肿瘤进展期间，由于过度增殖细胞在导管和小叶的管腔空间中积聚，乳腺的良好有序结构被破坏。 随着时间的推移，肿瘤细胞可以侵入基质，在那里它们可以进入脉管系统并扩散到整个身体的远端部位。 虽然诱导侵袭性生长是转移级联反应中的关键步骤，但乳腺癌细胞如何变得具有侵袭性仍然知之甚少。 使用器官型培养系统和动物模型，我们建议确定（1）细胞运动性是如何调节细胞内信号通路在集体入侵;（2）乳腺成纤维细胞如何诱导集体入侵和（3）肿瘤细胞亚群如何触发集体入侵。 破译乳腺癌侵袭的要求可以确定肿瘤和微环境中治疗干预的靶点。 公共卫生相关性：远处转移是几乎所有乳腺癌患者死亡的原因。 导致转移发展的关键步骤是肿瘤细胞侵入结缔组织。 我们将研究肿瘤细胞如何变得具有侵袭性，目的是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点。