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DCIS simulation -- unstable perinecrotic boundary

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Published on Oct 26, 2010

This is Video S2 in Macklin et al. (2012).

Agent-based simulation of ductal carcinoma in situ (DCIS), a type of breast cancer that is constrained to growth in the breast duct lumen by a basement membrane. Shown here: a simulation of 30 days' growth in a 1mm length of duct.

The mechanical and population dynamic parameters have been calibrated to patient-specific immunohistochemistry and other histologic measurements.

In this simulation, the ratio of oxygen uptake rates for proliferating:nonproliferating cells is 100:1. This leads to a very unstable perinecrotic boundary, and is evidence against such a drastic ratio.

Dark circles: cell nuclei
Green cells: proliferating cells (Ki-67 positive; S, G2, M, or G1)
Red cells: apoptosis cells (cleaved Caspase-3 positive)
Pale blue cells: quiescent cells (G0)
Dark grey cells: necrotic cells prior to lysis
Debris in centre of duct: necrotic cellular debris
Red dots in centre of duct: clinically-detectable microcalcifications

Method: Agent-based, lattice-free model. Cell velocities determined by balance of adhesive and repulsive forces. Each cell has a phenotypic state governed by stochastic processes derived from nonhomogeneous Poisson processes.

Source: Macklin et al., "Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS): From microscopic measurements to macroscopic predictions of clinical progression." J. Theor. Biol., 2012 (in press).

Preprint: http://www.MathCancer.org/Publication...
publisher: http://dx.doi.org/10.1016/j.jtbi.2012...

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