Stromal TGFbeta in tumor progression

描述(申请人提供)：目的是在分子、细胞和体内水平上进一步阐明转化生长因子β信号在肿瘤进展中的作用。根据以前发表的研究和初步数据，我们假设间质细胞中转化生长因子信号的干扰会损害正常的间质与上皮细胞的相互作用，并促进肿瘤的发展。我们将通过：1)确定间质-上皮相互作用中转化生长因子β信号的分子和细胞机制，以及2)确定间质细胞特异性转化生长因子β信号在乳腺肿瘤进展和转移中的作用。转化生长因子β或受体I型和II型的异常表达或活性与表现出转移表型的体内肿瘤模型和人类乳腺癌细胞有关。我们的研究将探讨基质细胞特异性转化生长因子β信号在肿瘤进展中的作用和机制，并将进一步促进抗肿瘤治疗的理解和发展。

DESCRIPTION (provided by applicant): The objective is to further elucidate role of transforming growth factor beta (TGF beta) signaling in tumor progression at the molecular, cellular and in vivo levels. Based on previously published studies and preliminary data, we hypothesize that disruption of TGF signaling in stromal cells impairs normal stromal:epithelial interactions and contributes to tumor progression. We will address this hypothesis by: 1) determining the molecular and cellular mechanisms of TGF beta signaling in stromal:epithelial interactions and 2) determining the role of stromal cell specific TGF beta signaling in mammary tumor progression and metastases. Aberrant expression or activity of TGF beta or receptors type I and type II have been linked to in vivo tumor models exhibiting metastatic phenotypes and to human breast cancer cells. Our research will address the function and mechanisms through which stromal cell specific TGF beta signaling specifically contributes to tumor progression, and will further contribute to the understanding and development of anti tumor therapies.