This overall goal of our Proposed Center is to use a physics-based approach towards understanding the evolution of cancer resistance. From an experimental point of view, this will be accomplished using the "microhabitat patch" (MHP) technology developed on a microfluidic chip platform at Princeton. This, experimental technique is central to all aspects of our proposal as it allows us to experimentally "tune" parameters which affect cell migration and evolution and then watch the evolution of interacting populations of cells as they move and evolve in space and time. The main focus of this proposed section of our Center is to rapidly extend this technology to mammalian cells (from initial studies in bacteria), and to develop additional capabilities for such MHP's for studying how cancer cells respond to stress. These include 2-dimensional or 3-dimenstional arrays in addition to 1-dimension, the ability to tune the coupling parameters between MHP's and between MHP's and food supplies as a function of time, and to adjust the local temperature as a function of time. We will also develop approaches for extracting cells from chips after evolution experiments for off-chip genomic analysis, and eventually methods for on-chip genomic analysis. Once these technologies and capabilities are invented and developed, they will be transferred to the Princeton Microfluidic Shared Resource (Section N4) so that all Center members (cancer biologists, e.g.) and external researchers such as those on pilot or transnetwork projects can use the new capabilities.

Public Health Relevance

The main focus of this proposed section of our Center is to rapidly extend this technology to mammalian cells (from initial studies in bacteria), and to develop additional capabilities for such MHP's for studying how cancer cells respond to stress.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143803-05
Application #
8535646
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
5
Fiscal Year
2013
Total Cost
$199,351
Indirect Cost
Name
Princeton University
Department
Type
DUNS #
002484665
City
Princeton
State
NJ
Country
United States
Zip Code
08544
Jung, Younghun; Decker, Ann M; Wang, Jingcheng et al. (2016) Endogenous GAS6 and Mer receptor signaling regulate prostate cancer stem cells in bone marrow. Oncotarget 7:25698-711
Han, Weijing; Chen, Shaohua; Yuan, Wei et al. (2016) Oriented collagen fibers direct tumor cell intravasation. Proc Natl Acad Sci U S A 113:11208-11213
Yumoto, Kenji; Eber, Matthew R; Wang, Jingcheng et al. (2016) Axl is required for TGF-β2-induced dormancy of prostate cancer cells in the bone marrow. Sci Rep 6:36520
Piotrowski-Daspit, Alexandra S; Tien, Joe; Nelson, Celeste M (2016) Interstitial fluid pressure regulates collective invasion in engineered human breast tumors via Snail, vimentin, and E-cadherin. Integr Biol (Camb) 8:319-31
Gascard, Philippe; Tlsty, Thea D (2016) Carcinoma-associated fibroblasts: orchestrating the composition of malignancy. Genes Dev 30:1002-19
Amend, Sarah R; Roy, Sounak; Brown, Joel S et al. (2016) Ecological paradigms to understand the dynamics of metastasis. Cancer Lett 380:237-42
van der Toom, Emma E; Verdone, James E; Pienta, Kenneth J (2016) Disseminated tumor cells and dormancy in prostate cancer metastasis. Curr Opin Biotechnol 40:9-15
Amend, Sarah R; Valkenburg, Kenneth C; Pienta, Kenneth J (2016) Murine Hind Limb Long Bone Dissection and Bone Marrow Isolation. J Vis Exp :
Lee, Eunsohl; Wang, Jingcheng; Yumoto, Kenji et al. (2016) DNMT1 Regulates Epithelial-Mesenchymal Transition and Cancer Stem Cells, Which Promotes Prostate Cancer Metastasis. Neoplasia 18:553-66
Pan, Deng; Roy, Somdutta; Gascard, Philippe et al. (2016) SOX2, OCT3/4 and NANOG expression and cellular plasticity in rare human somatic cells requires CD73. Cell Signal 28:1923-1932

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