Majority of cancer patients will die of metastases originating from disseminated tumor cells (DTCs), years or even decades after treatment. This suggests that DTCs survive in a dormant, nonproliferative state. However, because the biology of DTCs is poorly understood it is critical to ask basic mechanistic questions to further develop translational approaches. Our goal is to identify these mechanisms by combining powerful In vivo models and novel imaging and nano-device technologies available through this collaboration. This consortium provides unprecedented synergy to study dormancy and address three emphasis areas of this RFA: 1) tumor dormancy, activation of dormant cells and the tumor microenvironment (SAI), and dormancy in response to cancer treatment (SA2);2) imaging the tumor microenvironment during tumor metastasis, and dormancy (SAI), as well as in response to therapies (SA2) and 3) characterization and functional relevance of the tumor microenvironment extracellular matrix (ECM) and how tumor cells stroma interactions (i.e. niches) establish metastatic cell fate (SA2). We hypothesize that at least two scenarios influence DTC dormancy. Scenario 1: DTCs from invasive cancers activate stress signals in response to a growth-restrictive target organ microenvironment inducing dormancy. Scenario 2: therapy and/or microenvironmental stress conditions (e.g. hypoxia) acfing on primary tumor cells carrying a

Public Health Relevance

We will use novel imaging and nano-device technologies to tag, track and isolate disseminating tumor cells departing from primary tumors and proliferating or entering dormancy in target organs. We will discover their metabolic, genomic and transcription profiles to identity a cancer dormancy gene signature relevant to patients.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163131-03
Application #
8566805
Study Section
Special Emphasis Panel (ZCA1-SRLB-3)
Project Start
Project End
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
3
Fiscal Year
2013
Total Cost
$274,007
Indirect Cost
$37,897
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Szulczewski, Joseph M; Inman, David R; Entenberg, David et al. (2016) In Vivo Visualization of Stromal Macrophages via label-free FLIM-based metabolite imaging. Sci Rep 6:25086
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Wang, Yarong; Wang, Haoxuan; Li, Jiufeng et al. (2016) Direct visualization of the phenotype of hypoxic tumor cells at single cell resolution in vivo using a new hypoxia probe. Intravital 5:
Goossens, Nicolas; Hoshida, Yujin; Aguirre-Ghiso, Julio A (2015) Origin and interpretation of cancer transcriptome profiling: the essential role of the stroma in determining prognosis and drug resistance. EMBO Mol Med 7:1385-7
Sosa, Maria Soledad; Parikh, Falguni; Maia, Alexandre Gaspar et al. (2015) NR2F1 controls tumour cell dormancy via SOX9- and RAR?-driven quiescence programmes. Nat Commun 6:6170
Curran, Colleen S; Carrillo, Esteban R; Ponik, Suzanne M et al. (2015) Collagen density regulates xenobiotic and hypoxic response of mammary epithelial cells. Environ Toxicol Pharmacol 39:114-24

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