Determining the Functional Contribution of Prostate Tumor Microenvironment in Bon

在这个项目中，我们建议解决低氧微环境(TME)在前列腺癌进展和转移性骨病出现中的功能贡献。本项目使用项目1中产生的小鼠模型来研究缺氧、EMT和肌成纤维细胞代谢的影响，并在人类前列腺癌组织中验证这些发现。这样的研究将在合作斯卡登实验室(项目3)进行，该实验室将确定可能与骨转移相关的骨细胞成分。我们还建议详细评估癌细胞模拟间充质细胞类型和经历上皮向间充质转化(EMT)的能力的获得，以期收集信息以确定针对转移性前列腺癌的新的治疗靶点。

In this project, we propose to address the functional contribution of hypoxic microenvironment (TME) to the progression of prostate cancer and emergence of metastatic bone disease. This project use the mouse models generated in the Project 1 to study the influence of hypoxia, EMT and myofibroblasts metabolism and validate these finding in human prostate cancer tissue. Such studies will be performed in collaboration Scadden Laboratory (Project 3), which will determine the cellular components of the bone that likely cooperate with bone metastasis. We also propose to evaluate in detail the acquisifion of the ability of cancer cell to mimic mesenchymal cell types and undergo a program of epithelial to mesenchymal transition (EMT), in hopes of gathering information to identify new therapeutic targets against metastatic prostate cancer.