Matrigel signals abnormal development of Cape fur seal primary mammary cells, possibly through the activation of the TGFß pathway.

The Cape fur seal is a sea mammal, belonging to the Pinnipedia family, who presents an unusual model of lactation. Indeed, contrary to the other sea mammals, the body of the fur seal is not big enough to store bubbler layer allowing it to remain on-shore for a long period of time without eating. Thus, this animal feeds its pup on-shore only for few days before foraging alone at sea for up to 4 weeks (cycle carrying out for about 10 months). Interestingly, during this foraging time, the mammary gland does not enter into the involution process despite the absence of sucking, which normally induces in all the other species the signalling of programmed death of the epithelial cells, bringing about to the return of the mammary gland to a virgin-like stage. This ability to switch “on/off” its milk production makes this animal an original model for the study of mammary gland biology, especially for the transition lactation to involution. Nevertheless, this study requires the adjustment of an in vitro model because of the limits on in vivo studies due to ethical considerations. Currently, MatrigelTM, a gelatinous protein mixture secreted by mouse sarcoma, is a commonly used biomatrix for the growth and differentiation of bovine and mouse primary mammary cells into mammospheres; a 3-dimensional acinar structure resembling the secretory alveolus in the mammary gland. These cells grow as a monolayer when cultured on plastic. In contrast, mammary cells from the Cape fur seal produce their own matrix when cultured on plastic to form mammospheres. However, when these cells are cultured on Matrigel they develop a stellate-like phenotype. In order to better understand the extracellular matrix mediated signaling that leads to correct polarization of mammary cells and mammosphere formation and investigate the effect of Matrigel on seal mammary cell differentiation, we conducted a microarray analysis on mammary cells before culture, mammospheres and stellate structures. The results show that the stellate phenotype is characterized by an activation of genes for the TGF-ß pathway which is well known for its role in cell development, migration and matrix formation. Surprisingly, these results contrast data using the mouse model in which the TGF-ß pathway was up-regulated in mammary cells on plastic, presumably to stimulate the cells to produce a matrix required for mammosphere formation. The results suggest there is a factor in Matrigel, which signals abnormal development of seal mammary cells resulting in a loss of polarization which is probably due to an epithelial-mesenchymal transition known to be stimulated by TGF-ß pathway. Thus, cape fur seal represents a new model to study the specificity of the matrix in normal cellular development and better understand cell-matrix interactions and signaling, mediating cell polarization and differentiation.

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