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

基质细胞和基质-上皮细胞相互作用在乳腺肿瘤进展早期的作用：与风险的关系， 预防和治疗 基质-上皮相互作用在乳腺癌中的重要性早已被认识到，但 基质细胞在乳腺癌发生和发展的早期阶段的作用要差得多 定义了许多女性正常间质的生物学属性可能会导致 有利于乳腺癌的发生和发展和/或基质细胞可能具有不同的 对包括浸润前病变的上皮细胞（例如上皮细胞）的后续行为的影响 增生和原位癌。更好地理解基质细胞在正常乳腺中的作用 乳腺癌患者和非乳腺癌患者的组织，并更全面地了解它们在癌前病变中的作用。 乳腺病变不仅有助于我们了解这些细胞在乳腺癌早期阶段的作用， 乳腺肿瘤发生，但也可能提供新的分子靶点， 和预防因此，本项目的目标是更全面地了解 基质细胞和基质-上皮相互作用在乳腺肿瘤发生的早期阶段， 进展该项目有三个具体目标： 目标1.为了确定在人类乳腺组织样本中，基质表达与乳腺癌之间是否存在关联， 在已知存在上皮病变的乳腺癌中起作用的标志物 与乳腺癌风险增加有关，并确定是否有基质标记物可以 作为独立的风险指标，在妇女良性和浸润前乳腺病变。 目标2.为了确定来自乳腺癌患者未受累乳腺组织的基质细胞是否更多， 比基质细胞更有利于癌症发展的女性，无癌变基因和确定 这种基质细胞的表达特征。 目标3。为了确定靶向参与基质-上皮相互作用的基因和蛋白质是否可以 可能具有治疗价值。

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.