TY - JOUR
T1 - Tumor invasion optimization by mesenchymal-amoeboid heterogeneity
AU - Hecht, Inbal
AU - Bar-El, Yasmin
AU - Balmer, Frederic
AU - Natan, Sari
AU - Tsarfaty, Ilan
AU - Schweitzer, Frank
AU - Ben-Jacob, Eshel
N1 - Funding Information:
This work was supported by Marie Curie International Reintegration Grant within the 7th European Community Framework Programme; US - Israel Binational Science Foundation and the Tauber Family Foundation at Tel Aviv University; The National Science Foundation (NSF) Center for Theoretical Biological Physics Grant NSF PHY-1308264; The Cancer Prevention and Research Institute of Texas (CPRIT) Scholar Program of the State of Texas at Rice University.
PY - 2015/5/27
Y1 - 2015/5/27
N2 - Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs. They typically move in a dense environment, filled with other cells. In this work we study cooperative effects between neighboring cells of different types, migrating in a maze-like environment with directional cue. Using a computerized model, we measure the percentage of cells that arrive to the defined target, for different mesenchymal/amoeboid ratios. Wall degradation of mesenchymal cells, as well as motility of both types of cells, are coupled to metabolic energy-like resource level. We find that indirect cooperation emerges in mid-level energy, as mesenchymal cells create paths that are used by amoeboids. Therefore, we expect to see a small population of mesenchymals kept in a mostly-amoeboid population. We also study different forms of direct interaction between the cells, and show that energy-dependent interaction strength is optimal for the migration of both mesenchymals and amoeboids. The obtained characteristics of cellular cluster size are in agreement with experimental results. We therefore predict that hybrid states, e.g. epithelial-mesenchymal, should be utilized as a stress-response mechanism.
AB - Metastasizing tumor cells migrate through the surrounding tissue and extracellular matrix toward the blood vessels, in order to colonize distant organs. They typically move in a dense environment, filled with other cells. In this work we study cooperative effects between neighboring cells of different types, migrating in a maze-like environment with directional cue. Using a computerized model, we measure the percentage of cells that arrive to the defined target, for different mesenchymal/amoeboid ratios. Wall degradation of mesenchymal cells, as well as motility of both types of cells, are coupled to metabolic energy-like resource level. We find that indirect cooperation emerges in mid-level energy, as mesenchymal cells create paths that are used by amoeboids. Therefore, we expect to see a small population of mesenchymals kept in a mostly-amoeboid population. We also study different forms of direct interaction between the cells, and show that energy-dependent interaction strength is optimal for the migration of both mesenchymals and amoeboids. The obtained characteristics of cellular cluster size are in agreement with experimental results. We therefore predict that hybrid states, e.g. epithelial-mesenchymal, should be utilized as a stress-response mechanism.
UR - http://www.scopus.com/inward/record.url?scp=84930221932&partnerID=8YFLogxK
U2 - 10.1038/srep10622
DO - 10.1038/srep10622
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AN - SCOPUS:84930221932
SN - 2045-2322
VL - 5
JO - Scientific Reports
JF - Scientific Reports
M1 - 10622
ER -