Our overriding goal is to develop a quantitative model describing tumor cell dynamics and dissemination in the microcirculation. Meaningful output from our model is reliant upon the quality of the input variables: the physical and mechanical properties of cancer. However, surprisingly little quantitative information is known about the size, shape and feel of cancer in the fluid phase. Therefore, the first step toward the development of a model of cancer in the metastatic phase will be to establish the fundamental physical parameters of cancer cells in the circulation. Access to a unique population of tissue samples from colon and non-small lung cancer patients will provide us with the unique opportunity to characterize the physical properties of circulating tumor cells (CTCs).The physical models will be based on formulating the conservation of mass and momentum equations for a fluid-solid system in an incompressible flow regime. The solid (cancer cell) will be based on a deformable nonlinear shell model embedded within the flowfield, in a low Reynolds number regime. A newly developed version of the stochastic immersed boundary method will be used to simulate individual CTCs within the human vascular system in various channel geometries, as well as cell clusters via simple spring-mass systems. Mechanical properties of both the individual cell and cell aggregates will be closely correlated with the lab measured properties of the human samples obtained. We are not aware of any other group which is developing a fundamental model of cancer transit hand-in-hand with human samples. We will exploit this combined approach to establish a statistical model and fluid dynamics model for the behavior, survival, and destination of cancer in the vascular system.

Public Health Relevance

The modeling represents the first human-specimen based fluid-solid model of circulating cancer cells within the human vascular system. It will provide a unique view of the physical mechanisms at work in the metastatic phase of various cancers. In the process, we will develop a first-principle description of the disease, based on a mechanistic point of view.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Specialized Center--Cooperative Agreements (U54)
Project #
5U54CA143906-05
Application #
8568051
Study Section
Special Emphasis Panel (ZCA1-SRLB-9)
Project Start
Project End
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$309,577
Indirect Cost
$106,556
Name
Scripps Research Institute
Department
Type
DUNS #
781613492
City
La Jolla
State
CA
Country
United States
Zip Code
92037
Mitrugno, Annachiara; Tormoen, Garth W; Kuhn, Peter et al. (2016) The prothrombotic activity of cancer cells in the circulation. Blood Rev 30:11-9
Ruiz, Carmen; Li, Julia; Luttgen, Madelyn S et al. (2015) Limited genomic heterogeneity of circulating melanoma cells in advanced stage patients. Phys Biol 12:016008
King, Michael R; Phillips, Kevin G; Mitrugno, Annachiara et al. (2015) A physical sciences network characterization of circulating tumor cell aggregate transport. Am J Physiol Cell Physiol 308:C792-802
Phillips, Kevin G; Lee, Angela M; Tormoen, Garth W et al. (2015) The thrombotic potential of circulating tumor microemboli: computational modeling of circulating tumor cell-induced coagulation. Am J Physiol Cell Physiol 308:C229-36
Baker-Groberg, Sandra M; Phillips, Kevin G; Healy, Laura D et al. (2015) Critical behavior of subcellular density organization during neutrophil activation and migration. Cell Mol Bioeng 8:543-552
Rodriguez-Lee, Mariam; Kuhn, Peter; Webb, David R (2014) Advancing cancer patient care by integrating circulating tumor cell technology to understand the spatial and temporal dynamics of cancer. Drug Dev Res 75:384-92
Totonchy, Jennifer E; Clepper, Lisa; Phillips, Kevin G et al. (2014) CXCR7 expression disrupts endothelial cell homeostasis and causes ligand-dependent invasion. Cell Adh Migr 8:165-76
Carlsson, Anders; Nair, Viswam S; Luttgen, Madelyn S et al. (2014) Circulating tumor microemboli diagnostics for patients with non-small-cell lung cancer. J Thorac Oncol 9:1111-9
Newton, Paul K; Mason, Jeremy; Hurt, Brian et al. (2014) Entropy, complexity, and Markov diagrams for random walk cancer models. Sci Rep 4:7558
Bethel, Kelly; Luttgen, Madelyn S; Damani, Samir et al. (2014) Fluid phase biopsy for detection and characterization of circulating endothelial cells in myocardial infarction. Phys Biol 11:016002

Showing the most recent 10 out of 53 publications