Center on the Microenvironment and Metastasis

微环境和转移中心

• 批准号: 8704585
• 负责人: MICHAEL L SHULER
• 金额: $ 2.89万
• 依托单位: CORNELL UNIVERSITY
• 依托单位国家: 美国
• 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
• 来源: https://reporter.nih.gov/project-details/8704585
• 关键词: Adhesions; Blood Circulation; Blood Vessels; Buffaloes; Cancer Biology; Cancer Center; Candidate Disease Gene; Cells; Collaborations; Core Facility; Dimensions; Discipline; Distant; Drug Targeting; Engineering; Faculty; Generations; Genes; Growth; Home environment; Individual; Instruction; Intervention; Intervention Studies; Life; Malignant Neoplasms; Measurement; Metastatic Lesion; Methods; Microfabrication; Modeling; Modems; Molecular; Morbidity - disease rate; Neoplasm Circulating Cells; Neoplasm Metastasis; Normal Cell; Pathway interactions; Patients; Peripheral; Physics; Process; Research; Research Personnel; Scientist; Site; Testing; Tissues; Training; Universities; Ursidae Family; Work; base; cancer cell; cell growth; epigenomics; medical schools; mortality; nano; nanobiotechnology; nanofabrication; neoplastic cell; novel; oncology; physical process; physical science; three dimensional structure; tumor; tumor microenvironment

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，特别是在转移的建立和生长方面，阻碍了对肿瘤细胞与其非转化对应物的差异的全面理解。癌细胞迁移并存活。外周血流作为特定血管部位的归宿，以引发转移灶，并重新编程局部基质和诱导新血管生成，从而允许转移性病变的建立和生长。为了消除这种复杂性，并确定新的药理学靶点来抑制转移的启动和生长，我们将利用康奈尔大学在复杂的微纳米纤维方面的显著优势。这种方法将能够形成具有精确控制和“可调”尺寸的3D结构，以概括和定量测试转移性肿瘤微环境中的理化决定因素。该中心的物理科学研究人员汇集了最先进的小规模材料加工，物理测量和建模方法的杰出专业知识。物理科学和工程为基础的研究人员在这方面的努力是世界领先的纳米生物技术和使用的方法来探测生命过程中的细胞和分子水平。在本申请中，这些主要为物理科学实验而开发的方法将被调整并用于癌症研究，重点在于解剖通过与组织基质和新生肿瘤脉管系统的相互作用调节循环肿瘤细胞迁移、粘附和转移灶建立的分子机制。该团队与威尔医学院癌症中心和布法罗大学的主要癌症研究人员合作，将为了解肿瘤细胞（包括患者来源的循环肿瘤细胞）及其与定义的微环境的相互作用提供新的基础水平。这些研究将使用无偏见的基因和途径发现方法，而不是关注干预的候选基因，以促进预测癌症转移新干预措施的可行途径。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师的交叉培训，以教育新一代科学家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，以及新开发的微生物学和纳米生物学方法，将提供给物理科学肿瘤中心的研究人员，以丰富整个网络的合作和传播技术进步。通过这种方法，这项研究的影响应该比普通的个人研究项目更广泛地感受到。