Center on the Microenvironment and Metastasis

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非转化细胞的区别的全面理解。癌细胞迁移并存活于。外周血液是特定血管部位的家园，可以引发转移灶，并对局部基质进行重新编程，诱导新血管生成，从而允许转移灶的建立和生长。为了消除这种复杂性，并确定新的药理靶点来抑制转移的发生和生长，我们将利用康奈尔大学在复杂的微纳米制造方面的显著优势。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物理化学决定因素。该中心的物理科学研究人员汇集了最先进的小型材料加工，物理测量和建模方法的杰出专业知识。在这项工作中，物理科学和工程研究人员在纳米生物技术和使用方法在细胞和分子水平上探测生命过程方面处于世界领先地位。在本应用中，这些主要用于物理科学实验的方法将被应用于癌症研究，重点是解剖调节循环肿瘤细胞迁移、粘附和通过与组织基质和新生肿瘤血管的相互作用建立转移灶的分子机制。该团队将与威尔医学院癌症中心和布法罗大学的领先癌症研究人员合作，为肿瘤细胞（包括患者来源的循环肿瘤细胞）及其与特定微环境的相互作用提供新的基础认识。这些研究将使用无偏倚的基因和途径发现方法，而不是专注于干预的候选基因，以促进预测癌症转移新干预措施的可行途径。将强调对物理科学和癌症生物学学科的初级研究人员和教师进行交叉培训，以培养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，以及新开发的微纳米制造方法，将提供给物理科学肿瘤中心的研究人员，以丰富合作并在整个网络中传播技术进步。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。

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.