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.

Public Health Relevance

This PS-OC brings together expert teams from the fields of physics, nano and microfabrication, engineering and cancer biology to develop novel trans-disciplinary approaches to better understand the complexity of cancer metastasis, the aspect of cancer that directly leads to patient morbidity and mortality. Approaches developed by physical scientists will be focused on the study of cancer. Our studies aim to identify novel mechanisms used by cancer cells, but not normal cells, for growth and metastasis to distant body sites. These new mechanism provide novel drug targets, that aim towards arresting cancer metastasis.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143876-05
Application #
8534711
Study Section
Special Emphasis Panel (ZCA1-SRLB-9 (O1))
Program Officer
Eljanne, Mariam
Project Start
2009-09-28
Project End
2014-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$2,242,939
Indirect Cost
$811,625
Name
Cornell University
Department
Biology
Type
Organized Research Units
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Cao, Xuan; Moeendarbary, Emad; Isermann, Philipp et al. (2016) A Chemomechanical Model for Nuclear Morphology and Stresses during Cell Transendothelial Migration. Biophys J 111:1541-1552
McCoy, Michael G; Seo, Bo Ri; Choi, Siyoung et al. (2016) Collagen I hydrogel microstructure and composition conjointly regulate vascular network formation. Acta Biomater 44:200-8
Denais, Celine M; Gilbert, Rachel M; Isermann, Philipp et al. (2016) Nuclear envelope rupture and repair during cancer cell migration. Science 352:353-8
Duncan, Sara M; Seigel, Gail M (2016) High-contrast enzymatic immunohistochemistry of pigmented tissues. J Biol Methods 3:
Seigel, G M; Sharma, S; Hackam, A S et al. (2016) HER2/ERBB2 immunoreactivity in human retinoblastoma. Tumour Biol 37:6135-42
Chandrasekaran, Siddarth; Chan, Maxine F; Li, Jiahe et al. (2016) Super natural killer cells that target metastases in the tumor draining lymph nodes. Biomaterials 77:66-76
Wang, Suming; Blois, Anna; El Rayes, Tina et al. (2016) Development of a prosaposin-derived therapeutic cyclic peptide that targets ovarian cancer via the tumor microenvironment. Sci Transl Med 8:329ra34
Hall, Matthew S; Alisafaei, Farid; Ban, Ehsan et al. (2016) Fibrous nonlinear elasticity enables positive mechanical feedback between cells and ECMs. Proc Natl Acad Sci U S A 113:14043-14048
Bordeleau, Francois; Chan, Bryan; Antonyak, Marc A et al. (2016) Microvesicles released from tumor cells disrupt epithelial cell morphology and contractility. J Biomech 49:1272-9
Levin, Michael; Klar, Amar J S; Ramsdell, Ann F (2016) Introduction to provocative questions in left-right asymmetry. Philos Trans R Soc Lond B Biol Sci 371:

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