Morphogenic Responses of Mammary Epithelial Cells Grown in Biological Semi-Solid Substrates

Abstract

Morphogenetic movements of epithelial cells are critical to normal and pathological development of tissues and organs. Characteristically, epithelial cells are tightly connected through several junctional structures and this cohesiveness allows continuous lining in the body. During normal development, epithelial cells can modulate their cohesiveness to acquire diverse morphological forms for their specific functions, such as the thyroid follicles, the kidney tubules or the complex branching and alveolar structures found in the lung, salivary and mammary glands. These supracellular structures are not only determined by the genome of the cells, but are also governed by local molecular signals, such as growth factors, by adhesive interactions of epithelial cells with themselves or other cell types (cell-cell adhesion) or extra-cellular matrix substrates (cell-matrix adhesion) and by their function in the organism (for reviews see Bissel et al. [1] and Gumbiner [2]). The understanding of deregulated adhesive properties of epithelial cells is of major importance during tumor development, since more than 80% of the human tumors are epithelial in origin. It is assumed that the development of malignant tumors, in particular the transition from benign lesions to invasive, metastatic tumors, is characterized by the ability of a cancerous epithelial cell to overcome cell-cell adhesion and cell-substrate adhesion, and to invade surrounding tissue. Tumoral and metastatic development can therefore be described as the result of deregulated growth and adhesiveness, and increased invasiveness of epithelial cells.