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The growth of a tumour in a duct is examined in order to model ductal carcinoma in situ (DCIS) of the breast, the earliest known stage of breast cancer. Interactions between the expansive forces created by tumour cell proliferation and the stresses that develop in the compliant basement membrane are studied using numerical and analytical techniques. Particular attention focuses on the impact that proteolytic enzymes have on the tumour's progression. As the tumour expands and the duct wall deforms, the tumour cells are subjected to mechanical and nutritional stresses caused by high pressures and oxygen deprivation. Such stresses may stimulate the cells to produce proteolytic enzymes that degrade the duct wall, making it more compliant and prone to penetration by the tumour cells. We use our model to compare these two hypotheses for enzyme production and find that mechanical stress is likely the dominant mechanism, with the wall deforming most at the centre of the duct. We then discuss the biological implications of our theoretical results and suggest possible directions for future work.

Original publication

DOI

10.1016/j.jtbi.2004.08.032

Type

Journal article

Journal

J Theor Biol

Publication Date

21/02/2005

Volume

232

Pages

523 - 543

Keywords

Animals, Breast, Breast Neoplasms, Carcinoma in Situ, Carcinoma, Intraductal, Noninfiltrating, Disease Progression, Female, Humans, Models, Biological, Peptide Hydrolases, Stress, Mechanical