The Role of Stromal Cells and Stromal-Epithelial Interaction in the Early Stages

早期阶段基质细胞和基质-上皮相互作用的作用

• 批准号: 7729487
• 负责人: KORNELIA POLYAK
• 金额: $ 18.31万
• 依托单位: DANA-FARBER CANCER INST
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-01 至 2010-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7729487
• 关键词: Age; Archives; Behavior; Benign; Biological; Biological Assay; Breast; Breast Cancer Cell; Breast Cancer Treatment; Breast Carcinoma; Breast Diseases; CCL3 gene; CCL4 gene; CXCL12 gene; CXCL14 gene; CXCR4 Receptors; Cancer Patient; Cancerous; Carcinoma; Carcinoma in Situ; Cells; Clinical; Clinical Trials; Condition; Contralateral; Cytoskeleton; Data; Development; Endothelial Cells; Engineering; Epithelial; Epithelial Cells; Epithelial-Stromal Communication; Family history of; Fc Receptor; Fibroblasts; Future; Gene Expression Profile; Gene Proteins; Genes; Goals; Growth; Histologic; Human; Hyperplasia; Immunohistochemistry; In Vitro; Inflammatory; Invasive; Invasive Lesion; Ipsilateral; Lesion; Malignant Neoplasms; Mammary Gland Parenchyma; Mammary Neoplasms; Molecular Profiling; Molecular Target; Myofibroblast; Neoadjuvant Therapy; Neoplastic Epithelial Cell; Noninfiltrating Intraductal Carcinoma; Numbers; Paracrine Communication; Patients; Pericytes; Play; Premalignant; Prevention; RNA Interference; Risk; Role; Sampling; Source; Staging; Standards of Weights and Measures; Stromal Cells; Testing; Therapeutic; Therapeutic Agents; Tissue Microarray; Tissue Sample; Tumorigenicity; Woman; Xenograft procedure; base; breast lesion; cancer risk; cell type; chemokine; cohort; design; follow-up; in vivo; inhibitor/antagonist; malignant breast neoplasm; novel therapeutics; paracrine; receptor; serial analysis of gene expression; small molecule; therapeutic target; tumor; tumor initiation; tumor progression; tumorigenesis; tumorigenic

THE ROLE OF STROMAL CELLS AND STROMAL-EPITHELIAL INTERACTION IN THE EARLY STAGES OF BREAST TUMOR PROGRESSION: IMPLICATIONS FOR RISK, PREVENTION AND TREATMENT The importance of stromal-epithelial interactions in established breast cancers has long been recognized, but the role of stromal cells in the early stages of breast cancer initiation and progression are much less well defined. It is possible that biological attributes of the normal stroma in many women may create conditions that favor the inception and progression of mammary carcinomas and/or that stromal cells may have distinct effects on the subsequent behavior of the epithelial cells that comprise pre-invasive lesions, such as epithelial hyperplasias and carcinomas in situ. A better understanding of the role of stromal cells in normal breast tissue from patients with and without breast cancer and a more complete appreciation of their role in precancerous breast lesions would not only help us understand the part these cells play in the early stages of breast tumorigenesis, but would also likely provide new molecular targets both for breast cancer treatment and prevention. The goals of this project, therefore, are to obtain a more complete understanding of the role of stromal cells and of stromal-epithelial interactions in the early stages of breast tumor initiation and progression. This project has three specific aims: Aim 1. To determine in human breast tissue samples if there is an association between expression of stromal markers that appear to have a role in established breast cancers with the presence of epithelial lesions known to be associated with increased breast cancer risk, and to determine if there are stromal markers that can be used as independent risk indicators in women with benign and pre-invasive breast lesions. Aim 2. To determine if stromal cells from uninvolved breast tissue from patients with breast cancer are more conducive to cancer development than stromal cells of women, without cancer and to determine the gene expression signatures of such stromal cells. Aim 3. To determine if targeting of genes and proteins involved in stromal-epithelial interactions could potentially be of therapeutic value.

基质细胞和基质-上皮相互作用在乳腺肿瘤进展早期的作用：对风险的影响