Follicle-like structure and polarized monolayer: role of the extracellular matrix on thyroid cell organization in primary culture.

The thyroid follicle, the morphofunctional unit of thyroid gland, is a spheroidal structure formed by a monolayer of polarized cells surrounding a closed cavity in which thyroglobulin accumulates. Newly isolated porcine thyroid cells reorganize into two types of structures which differ by the orientation of cell polarity: in follicle-like structures, obtained in the presence of TSH, the apical pole delineates a closed cavity and cells express most parameters characteristic of thyroid function; in inside-out follicles the apical pole is oriented towards the culture medium and cells do not express properly the thyroid function. The organization of newly formed follicles can be modified by stimulation of cell migration or by interaction of their apical poles with a new cell environment. Seeded on a hard surface (glass, plastic), cells of follicle-like structures or inside-out follicles formed in suspension migrate giving a monolayer. On the contrary, cells organized into a monolayer treated with hexamethylene bisacetamide, reorganize into follicle-like structures. Inside-out structures reorganize upon interaction of their apical poles with collagen I gel, a coherent matrix, or with a reconstituted basement membrane (RBM), a soft matrix. Overlaid with collagen I, monolayers reorganize into follicles. Embedded in collagen I or in RBM, inside-out follicles reorient their polarity giving functional follicles. On the RBM surface, cells pull on the gel and embed themselves in the soft matrix gel, finally reorienting their polarity to inside-in polarity. When comparing thyroid cells with other epithelial cell types (mammary cells, Sertoli cells), it appears that the obtention in culture of follicle-like structures, i.e. closed inside-in polarized cell organization, is the best way to express in culture both morphology and function of any specific epithelial tissue, the polarized monolayer in porous bottom culture chamber coming just behind.