title: A 2D mechanistic model of breast ductal carcinoma in situ (DCIS) morphology and progression.
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.
authors.affiliation: BioMaPS Institute, Rutgers University, Piscataway, NJ 08854, USA. kerrin@eden.rutgers.edu
authors.forename: Kerri-Ann
authors.initials: KA
authors.lastname: Norton
authors.forename: Michael
authors.initials: M
authors.lastname: Wininger
authors.forename: Gyan
authors.initials: G
authors.lastname: Bhanot
authors.forename: Shridar
authors.initials: S
authors.lastname: Ganesan
authors.forename: Nicola
authors.initials: N
authors.lastname: Barnard
authors.forename: Troy
authors.initials: T
authors.lastname: Shinbrot
mesh_terms: D017209:Apoptosis; D001943:Breast Neoplasms / Q000473:pathology*; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000473:pathology*; D003661:Decision Support Techniques; D018450:Disease Progression; D005260:Female; D006801:Humans; D021621:Imaging, Three-Dimensional; D008495:Medical Oncology / Q000379:methods; D008953:Models, Anatomic; D008954:Models, Biological; D008962:Models, Theoretical; D009336:Necrosis; D012984:Software; D013997:Time Factors