TUMOR MICROENVIRONMENT & METASTASIS PROGRAM

肿瘤微环境和转移项目的目标是了解肿瘤微环境的分子生物学机制。 参与调节肿瘤细胞存活、分化和功能的机制， 负责侵袭和转移的微环境以及所采用的信号传导途径。程序 是由一个计划项目赠款的支持，重点是定义如何在巨噬细胞和 癌细胞有助于产生侵袭性表型的运动和趋化行为。 研究的主要疾病部位是乳腺癌，但也包括其他癌症，如肺癌。该计划已 三个主要目标：（1）剖析微环境在肿瘤进展中的作用， 转移：强调肿瘤细胞和肿瘤相关细胞之间的相互作用。 巨噬细胞，促进肿瘤进展和转移的细胞。这些研究利用异种移植， 小鼠模型以及人肿瘤异种移植到免疫受损小鼠中。六个不同 巨噬细胞在促进恶性肿瘤中的功能已经被鉴定。2)的分子机制 生长因子和激素在调节细胞运动和增殖中的作用。研究人员研究了 在调节细胞运动性、趋化性、侵袭性以及 细胞增殖特别强调来自殖民地刺激因子受体的信号传导， 巨噬细胞和ErbB家族的受体在肿瘤细胞中的作用，研究利用了 这些研究包括细胞培养和异种移植系统，以及乳腺癌小鼠模型。第三章 成像和动物模型。这是针对创新的光学技术的发展， 多光子显微镜成像细胞和它们在体内肿瘤微环境中的相互作用 再加上创新的小鼠遗传学来标记谱系和干扰信号通路。 目前有来自10个部门的21名计划成员，其中16名是主要成员， 由17个NCI（290万美元直接）和10个其他NIH赠款支持。已经有8个新成员加入了这个团队 程序.自上一次CCSG审查以来，已有246篇癌症相关研究论文， 其中20%是计划内的，21%是计划间的。 合作。

The objective of the Tumor Microenvironment and Metastasis Program is to understand the molecular mechanisms involved in the regulation of the survival, differentiation and function of cells in tumors, the microenvironments responsible for invasion and metastasis, and signaling pathways employed. The program is supported by a Program Project grant focused on defining how signaling pathways in macrophages and carcinoma cells contribute to the motility and chemotatic behaviors that generate the invasive phenotype. The major disease site studied is breast but other cancers such as lung are also included. The program has three major goals: (1) Dissection of the role the microenvironment plays in tumor progression and metastasis: There is an emphasis on the interaction between tumor cells and tumor associated macrophages, cells that promote tumor progression and metastasis. These studies utilize, xenotransplants, mouse models, as well as human tumor xenotransplants into immunocompromised mice. Six distinct functions have been identified for macrophages in promoting malignancy. 2) The molecular mechanisms of growth factor and hormone action in regulating cell motility and proliferation. Investigators study the intrinsic mechanisms that feed downstream from receptors in regulating cell motility, chemotaxis, invasion as well as cell proliferation. There is a particular emphasis on signaling from the colony stimulating factor receptor in macrophages and the ErbB family of receptors in tumor cells and the studies utilize a combination of systems, including cell lines in culture and as xenografts, as well as mouse models of breast cancer. 3) Imaging and animal models. This is directed to the development of innovative optical technologies using multiphoton microscopy to image cells and their interactions within the tumor microenvironment in vivo coupled with innovative mouse genetics to label lineages and perturb signaling pathways. There are currently 21 program members from 10 departments, of whom 16 are primary members, supported by 17 NCI ($2.9M Direct) and 10 other NIH grants. There have been 8 new recruits to this program. Since the last CCSG review there have been 246 cancer-relevant research papers by members of this program of which 20% represent intraprogrammatic, and 21% represent interprogrammatic collaborations.