The overarching theme of this proposal is "Impact of Tumor Heterogeneity on Cancer Progression". The Experimental Component is therefore geared to quantifying cancer cell heterogeneity with respect to hallmark traits of cancer progression, such as proliferation, metabolism and motility. We will quantify this trait heterogeneity in model cultured cell lines, under several mE perturbation, as average and distribution measurements performed at the single-cell level by high-content automated microscopy and image processing. Trait distributions will also be resolved as statistical subpopulations, in order to uncover common trends between cell lines. Several In vivo tumor experimental systems will complement in vitro assays for the purpose of theoretical model validation. We have assembled a team of talented experimentalists that cover all specific skills needed for this Component, as shown by their distinguished publication records. Staff scientists will assure continuity of Component technology.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA113007-10
Application #
8628755
Study Section
Special Emphasis Panel (ZCA1-SRLB-C)
Project Start
Project End
Budget Start
2014-03-01
Budget End
2015-02-28
Support Year
10
Fiscal Year
2014
Total Cost
$170,230
Indirect Cost
$29,863
Name
Vanderbilt University Medical Center
Department
Type
DUNS #
004413456
City
Nashville
State
TN
Country
United States
Zip Code
37212
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Scott, Jacob G; Hjelmeland, Anita B; Chinnaiyan, Prakash et al. (2014) Microenvironmental variables must influence intrinsic phenotypic parameters of cancer stem cells to affect tumourigenicity. PLoS Comput Biol 10:e1003433
Poleszczuk, Jan; Enderling, Heiko (2014) A High-Performance Cellular Automaton Model of Tumor Growth with Dynamically Growing Domains. Appl Math (Irvine) 5:144-152
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Scott, Jacob G; Basanta, David; Anderson, Alexander R A et al. (2013) A mathematical model of tumour self-seeding reveals secondary metastatic deposits as drivers of primary tumour growth. J R Soc Interface 10:20130011
Hoshino, Daisuke; Branch, Kevin M; Weaver, Alissa M (2013) Signaling inputs to invadopodia and podosomes. J Cell Sci 126:2979-89
Bryce, Nicole S; Reynolds, Albert B; Koleske, Anthony J et al. (2013) WAVE2 regulates epithelial morphology and cadherin isoform switching through regulation of Twist and Abl. PLoS One 8:e64533
Rejniak, Katarzyna A; Quaranta, Vito; Anderson, Alexander R A (2012) Computational investigation of intrinsic and extrinsic mechanisms underlying the formation of carcinoma. Math Med Biol 29:67-84
Basanta, D; Scott, J G; Fishman, M N et al. (2012) Investigating prostate cancer tumour-stroma interactions: clinical and biological insights from an evolutionary game. Br J Cancer 106:174-81
Kam, Yoonseok; Rejniak, Katarzyna A; Anderson, Alexander R A (2012) Cellular modeling of cancer invasion: integration of in silico and in vitro approaches. J Cell Physiol 227:431-8

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