Journal Article

Computational investigation of intrinsic and extrinsic mechanisms underlying the formation of carcinoma

Katarzyna A. Rejniak, Vito Quaranta and Alexander R. A. Anderson

in Mathematical Medicine and Biology: A Journal of the IMA

Published on behalf of Institute of Mathematics and its Applications

Volume 29, issue 1, pages 67-84
Published in print March 2012 | ISSN: 1477-8599
Published online November 2010 | e-ISSN: 1477-8602 | DOI:
Computational investigation of intrinsic and extrinsic mechanisms underlying the formation of carcinoma

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The disruption of tissue epithelial architecture is thought to be involved in the initiation of cancer; however, little is known about the cell biology of early neoplastic lesions. Computational models can facilitate in the study of early cancer stagesby simulating different scenarios of tumour inception and by testing in silico the influence of various intrinsic and extrinsic factors on the emerging multicellular morphologies. Here, we have used a computational model to create 3D morphocharts, collections of multicellular morphologies arising from systematic modification of three model parameters defining cell sensitivity to external cues for cell growth, death and adhesion to the extracellular matrix. This systematic search revealed the ranges of parameter values for which robust epithelial structures formed and those that led to abnormal geometrical forms resembling tumour-like morphologies. We also showed how our model can be used to map morphologies of experimental multicellular systems onto their in silico counterpart via the cell sensitivity parameter space that may in turn allow us to identify genetic or epigenetic changes responsible for these morphological distortions.

Keywords: development of epithelial tumours; formation of mutant acini; single-cell-based models; immersed boundary method; self-organization; robustness; morphology classification

Journal Article.  0 words. 

Subjects: Applied Mathematics ; Biomathematics and Statistics

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