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 #
5U54CA143876-04
Application #
8309484
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
2012-08-01
Budget End
2013-07-31
Support Year
4
Fiscal Year
2012
Total Cost
$2,403,199
Indirect Cost
$1,017,817
Name
Cornell University
Department
Biology
Type
Organized Research Units
DUNS #
872612445
City
Ithaca
State
NY
Country
United States
Zip Code
14850
Carey, Shawn P; Martin, Karen E; Reinhart-King, Cynthia A (2017) Three-dimensional collagen matrix induces a mechanosensitive invasive epithelial phenotype. Sci Rep 7:42088
Song, Young Hye; Warncke, Christine; Choi, Sung Jin et al. (2017) Breast cancer-derived extracellular vesicles stimulate myofibroblast differentiation and pro-angiogenic behavior of adipose stem cells. Matrix Biol 60-61:190-205
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
Davison, Angus; McDowell, Gary S; Holden, Jennifer M et al. (2016) Formin Is Associated with Left-Right Asymmetry in the Pond Snail and the Frog. Curr Biol 26:654-60
Duncan, Sara M; Seigel, Gail M (2016) High-contrast enzymatic immunohistochemistry of pigmented tissues. J Biol Methods 3:
Wayne, Elizabeth C; Chandrasekaran, Siddarth; Mitchell, Michael J et al. (2016) TRAIL-coated leukocytes that prevent the bloodborne metastasis of prostate cancer. J Control Release 223:215-223
Carey, Shawn P; Goldblatt, Zachary E; Martin, Karen E et al. (2016) Local extracellular matrix alignment directs cellular protrusion dynamics and migration through Rac1 and FAK. Integr Biol (Camb) 8:821-35
McDowell, G S; Philpott, A (2016) New Insights Into the Role of Ubiquitylation of Proteins. Int Rev Cell Mol Biol 325:35-88
Li, Jiahe; Sharkey, Charles C; Wun, Brittany et al. (2016) Genetic engineering of platelets to neutralize circulating tumor cells. J Control Release 228:38-47
Dimonte, Alice; Adamatzky, Andrew; Erokhin, Victor et al. (2016) On chirality of slime mould. Biosystems 140:23-7

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