We hypothesize that dense collagen matrices create a mechanical "stress" environment that alters cellular invasion and cellular metabolism, and promotes, depending on the ECM composition, proliferation or dormancy at metastatic target sites. We propose that changes in the fluorescence lifetime of NAD(P)H and FAD can be used 1) in the research setting to track and understand disease progression, macrophage infiltration, disseminated tumor cells (DTCs) and dormancy;and 2) developed for use in the clinical setting to provide early information about tumor progression and dissemination. NAD(P)H and FAD are particularly attractive potential biomarkers for clinical use, as they are endogenous signals that require no external label and can be imaged in fresh or fixed biopsy samples. These questions will be addressed in three specific aims: 1) Determine whether local regions of increased stress (mechanical, hypoxic or hypoglycemic) alter the metabolic signature of tumor and stromal cells;2) Investigate mechanisms by which fibrosis affects the dormancy and metabolic signatures of DTCs;3) Determine whether metabolic and dormancy signatures are useful predictors of stage and outcome in human HNSCC and breast cancer patients.

Public Health Relevance

We hypothesize that dense collagen matrices create a mechanical stress environment that alters cellular invasion and cellular metabolism, and promotes, depending on the ECM composition, proliferation or dormancy at metastatic target sites. We propose that changes in the fluorescence lifetime of NAD(P)H and FAD can be used 1) in the research setting to track and understand disease progression, macrophage infiltration, disseminated tumor cells (DTCs) and dormancy;and 2) developed for use in the clinical setting to provide early information about tumor progression and dissemination. In this project we will study these issues.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA163131-04
Application #
8708783
Study Section
Special Emphasis Panel (ZCA1-SRLB-3)
Project Start
Project End
Budget Start
2014-08-01
Budget End
2015-07-31
Support Year
4
Fiscal Year
2014
Total Cost
$253,397
Indirect Cost
$42,208
Name
Albert Einstein College of Medicine
Department
Type
DUNS #
110521739
City
Bronx
State
NY
Country
United States
Zip Code
10461
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Sosa, Maria Soledad; Bragado, Paloma; Debnath, Jayanta et al. (2013) Regulation of tumor cell dormancy by tissue microenvironments and autophagy. Adv Exp Med Biol 734:73-89
Begley, Ulrike; Sosa, Maria Soledad; Avivar-Valderas, Alvaro et al. (2013) A human tRNA methyltransferase 9-like protein prevents tumour growth by regulating LIN9 and HIF1-*. EMBO Mol Med 5:366-83
Aguirre-Ghiso, Julio A; Bragado, Paloma; Sosa, Maria Soledad (2013) Metastasis awakening: targeting dormant cancer. Nat Med 19:276-7

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