Stromal TGFbeta in tumor progression

描述（由申请人提供）：目的是在分子、细胞和体内水平进一步阐明转化生长因子β (TGF β)信号在肿瘤进展中的作用。根据先前发表的研究和初步数据，我们假设基质细胞中TGF信号的破坏会损害正常的基质与上皮的相互作用，并有助于肿瘤的进展。我们将通过：1)确定TGF β信号在基质上皮相互作用中的分子和细胞机制，以及2)确定基质细胞特异性TGF β信号在乳腺肿瘤进展和转移中的作用来解决这一假设。TGF β或I型和II型受体的异常表达或活性与具有转移表型的体内肿瘤模型和人类乳腺癌细胞有关。我们的研究将揭示基质细胞特异性TGF β信号对肿瘤进展的作用和机制，并将进一步促进对抗肿瘤治疗方法的理解和发展。

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.