Modelling glandular epithelial cancers in three-dimensional cultures

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Abstract
Epithelial cells grown in 3D cultures recapitulate numerous features of the glandular epithelium in vivo. These include the formation of cyst-like spheroids with a hollow lumen, apicobasal polarization of the cells comprising these structures, tight control of cell growth and proliferation, and the establishment of a basement membrane. Filling of the lumen with cells is a salient feature of early glandular epithelial cancers that remains poorly understood. Studies in 3D cultures have uncovered multiple processes and regulatory molecules that are involved in the formation and maintenance of luminal space. Known cancer genes give rise to a diverse array of morphogenetic phenotypes in 3D cultures that resemble important histopathological features observed in epithelial cancers in vivo. Apicobasal cell polarity is a fundamental characteristic of the glandular epithelium both in vivo and in vitro. Recent studies in 3D systems illustrate the importance of this process for an intact architecture. Various invasive properties have been observed in 3D systems, including invasion through the basement membrane. Future efforts directed towards co-culture systems that more faithfully represent the histological complexity of epithelial tissue in vivo are crucial for our understanding of epithelial cancers.