Lattice-based model of ductal carcinoma in situ suggests rules for XXXX progression to an invasive state.

@entity5 @entity3821 @entity0 @entity39
@entity3821 ( @entity3821 ) is a heterogeneous group of non-invasive lesions of the breast that result from abnormal proliferation of mammary epithelial cells. Pathologists characterize @entity3821 by four tissue morphologies (micropapillary, cribriform, solid, and comedo), but the underlying mechanisms that distinguish the development and progression of these morphologies are not well understood. Here we explored the conditions leading to the emergence of the different morphologies of @entity3821 using a two-dimensional multi-cell lattice-based model that incorporates cell proliferation, apoptosis, @entity39 , adhesion, and contractility. We found that the relative rates of cell proliferation and apoptosis governed which of the four morphologies emerged. High proliferation and low apoptosis favored the emergence of solid and comedo morphologies. In contrast, low proliferation and high apoptosis led to the micropapillary morphology, whereas high proliferation and high apoptosis led to the cribriform morphology. The natural progression between morphologies cannot be investigated in vivo since lesions are usually surgically removed upon detection; however, our model suggests probable transitions between these morphologies during @entity0 progression. Importantly, cribriform and comedo appear to be the ultimate morphologies of @entity3821 . Motivated by previous experimental studies demonstrating that @entity5 cells behave differently depending on where they are located within the mammary duct in vivo or in engineered tissues, we examined the effects of tissue geometry on the progression of @entity3821 . In agreement with our previous experimental work, we found that cells are more likely to invade from the end of ducts and that this preferential invasion is regulated by cell adhesion and contractility. This model provides additional insight into @entity5 cell behavior and allows the exploration of phenotypic transitions not easily monitored in vivo.
