Center on the Microenvironment and Metastasis

微环境和转移中心

基本信息

批准号：
8309484
负责人：
MICHAEL L SHULER
金额：
$ 240.32万
依托单位：
CORNELL UNIVERSITY
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-09-28 至 2014-07-31
项目状态：
已结题

项目摘要

The complexity of cancer, particularly in the establishment and growth of metastases, has hampered a comprehensive understanding of how tumor cells differ from their non-transformed counterparts. Cancer cells migrate and survive in. the peripheral bloodstream, home to specific vascular sites to initiate metastatic foci, and reprogram local stroma and induce neoangiogenesis to, permit establishment and growth of metastatic lesions. To deconvolute this complexity and to identify new pharmacological targets to inhibit metastasis initiation and growth, we will draw on our significant strengths in sophisticated micro and nanofabrication at Cornell University. This approach will enable the formation of 3D structures with precisely controlled and "tunable" dimensions to recapitulate and quantitatively test physicochemical determinants in the metastatic tumor microenvironment. The physical science researchers in this center bring together outstanding expertise in the most modem approaches for small scale materials processing, physical measurements and modeling. The physical science and engineering based researchers in this effort are among he world's leaders in nanobiotechnology and in the use of methods to probe life processes at the cellular and molecular level. In this application, these approaches, developed primarily for physical science experimentation, will be adapted and brought to bear on the study of cancer, with an emphasis on dissecting the molecular mechanisms that regulate circulating tumor cell migration, adhesion and the establishment of metastatic foci via interactions with tissue stroma and the nascent tumor vasculature. Working together with leading cancer investigators at Weill Medical College Cancer Center and the University of Buffalo, this team will inform a new fundamental level of understanding of tumor cells, including patient-derived circulating tumor cells, and their interaction with defined microenvironments. Rather than focusing on candidate genes for intervention, these studies will use unbiased gene and pathway discovery approaches to facilitate prediction of viable pathways for novel interventions in cancer metastasis. Cross-training of junior investigators and faculty across physical science and cancer biology disciplines will be emphasized, to educate a new generation of scientist to explore the scientific basis of cancer. New core facilities, including selected cell epigenomic analysis, and newly developed methods in micro and nanofabrication be made available to researchers of Physical Sciences Oncology Centers to enrich collaborations and disseminate technological advances throughout the network. By this approach the impact of this research should be felt far more widely than ordinary individual investigator projects.

癌症的复杂性，尤其是在转移的建立和生长中，已经阻碍了人们对肿瘤细胞如何与未转化的对应物不同的全面了解。癌细胞迁移并生存。外围血液是特定的血管部位的所在地，以启动转移性灶，并重新编程局部基质并诱导新血管生成，允许转移性病变的建立和生长。为了解散这种复杂性，并确定了抑制转移开始和生长的新药理靶标，我们将利用康奈尔大学在复杂的微型和纳米制作方面的重要优势。这种方法将使3D结构具有精确控制和“可调”维度的3D结构，以概括和定量测试转移性肿瘤微环境中的物理化学决定因素。该中心的物理科学研究人员在小规模材料处理，物理测量和建模的最调制器方法方面汇集了出色的专业知识。在这项工作中，基于物理科学和工程的研究人员是他在纳米生物技术领域的世界领导者之一，并使用方法来探测细胞和分子水平的生命过程。在此应用中，这些方法主要是为物理科学实验开发的，它将被调整并在癌症的研究中进行，重点是解剖分子机制，这些分子机制通过与组织层状肿瘤和新生肿瘤的相互作用来调节循环肿瘤细胞迁移，粘附和转移性焦点的建立。该团队与威尔医学院癌症中心和布法罗大学的领先癌症研究者合作，将为包括患者衍生的循环肿瘤细胞以及与定义的微环境的相互作用提供对肿瘤细胞的新基本了解。这些研究不是专注于候选基因进行干预，而是使用公正的基因和途径发现方法来促进对癌症转移新干预措施的可行途径的预测。将强调跨物理科学和癌症生物学学科的初级研究人员和教职员工的交叉培训，以教育新一代的科学家来探索癌症的科学基础。新的核心设施，包括选定的细胞表观基因组分析以及新开发的微型和纳米制作方法，可供物理科学肿瘤学中心的研究人员使用，以丰富整个网络的协作并传播技术进步。通过这种方法，这项研究的影响应比普通个人调查员项目更广泛。