Apical polarity in three-dimensional culture systems: where to now?

Abstract

Delineation of the mechanisms that establish and maintain the polarity of epithelial tissues is essential to understanding morphogenesis, tissue specificity and cancer. Three-dimensional culture assays provide a useful platform for dissecting these processes but, as discussed in a recent study in BMC Biology on the culture of mammary gland epithelial cells, multiple parameters that influence the model must be taken into account.

Figure 1

Architecture and morphology of the mammary gland. (a) A cartoon representation of the structure of the epithelial tissue of the human mammary gland indicating a large duct branching into a lobule. (b) A representation of a cross section cut through the bilayered epithelia: many bilaryered acini that are part of the lobule would be apparent yet their direct connection to the lobule 'disappears' in the 2D cross section. (c) A magnified cross section of the terminal ductal lobular unit (TDLU) referred to as an acinus. Acinar polarity is demonstrated where apical proteins face the lumen formed by luminal epithelial cells and the basement membrane (BM) is in contact with myoepithelial cells (d) S1 cultured cells form a single layered acinus-like structure in 3D culture with apico-basal polarity despite the lack of the myoepithelial layer.

Figure 2

Organization of basement membrane superstructure. A simplified and hypothetical diagram showing how BM might be assembled at the surface of a cell or an acinus. (a) Top: acinus surrounded by laminin-111 (green). Bottom: the laminin-111 polymerizes and engages integrins (blue) on the basal face of the epithelial cells. However, the laminin-111 polymer is not stably anchored into a supramolecular structure. In this case, apical polarity is not established and tight-junction proteins (pink) do not get organized on the apical surface of the acini. (b) Laminin-111 polymer (green) is anchored by type IV collagen (red); co-localization of the two proteins is shown by yellow. The proteins are now physically connected by nidogen (black). Basal integrins (blue) are organized and are likely to be held in a spatial orientation that allows proper signaling for establishment of apical polarity. Tight-junction proteins become organized apically in the acinus, and apical polarity is established.