A 2D mechanistic model of breast ductal carcinoma in situ (DCIS) morphology and progression |
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Authors: | Kerri-Ann Norton Michael Wininger Gyan Bhanot Shridar Ganesan |
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Institution: | a BioMaPS Institute, Rutgers University, Piscataway, NJ 08854, USA b Biomedical Engineering, Rutgers University, Piscataway, NJ 08854, USA c Clinical Brain Disorders Branch, National Institute of Mental Health, Bethesda, MD 20817, USA d Department of Molecular Biology and Biochemistry, Rutgers University, Piscataway, NJ 08854, USA e Department of Physics, Rutgers University, Piscataway, NJ 08854, USA f Simons Center for Systems Biology, Institute for Advanced Study, Princeton, NJ 08540, USA g Cancer Institute of New Jersey, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA h Department of Pathology, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ 08903, USA |
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Abstract: | Ductal carcinoma in situ (DCIS) of the breast is a non-invasive tumor in which cells proliferate abnormally, but remain confined within a duct. Although four distinguishable DCIS morphologies are recognized, the mechanisms that generate these different morphological classes remain unclear, and consequently the prognostic strength of DCIS classification is not strong. To improve the understanding of the relation between morphology and time course, we have developed a 2D in silico particle model of the growth of DCIS within a single breast duct. This model considers mechanical effects such as cellular adhesion and intra-ductal pressure, and biological features including proliferation, apoptosis, necrosis, and cell polarity. Using this model, we find that different regions of parameter space generate distinct morphological subtypes of DCIS, so elucidating the relation between morphology and time course. Furthermore, we find that tumors with similar architectures may in fact be produced through different mechanisms, and we propose future work to further disentangle the mechanisms involved in DCIS progression. |
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Keywords: | Tumor growth parameters Ductal morphology Computational model Breast cancer |
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