Epithelial Mesanchymal Interactions

The contribution of epithelia-mesenchyme interaction to normal development (eg., tissue formation) and to neoplasia has become a subject of increasing interest to scientists because of recent progress in deciphering the molecular signals that mediate this interaction. Clearly, some of the same types of molecules (eg., growth factors and their receptors, proteolytic enzymes, cell adhesion molecules, and structural proteins of the extracellular matrix) mediate exchange of information between epithelia and mesenchyme during normal development and malignant growth. However, defects in the regulation of this exchange appear to contribute to malignancy by allowing growth promoting, invasogenic, and angiogenic factors to accumulate within the microenvironment of the tumor. For example, recent studies suggest that abnormal interactions between tumor epithelial cells and stromal mesenchymal cells contribute to the overproduction and accumulation of scatter factor (hepatocyte growth factor), an invasogenic and angiogenic cytokine, in certain types of tumor. The production and and activation of type IV collagenase, a matrix-degrading enzyme required for tumor cell invasion, appears to require intimate cooperation between tumor and stromal cells. The material contained in this volume highlights the state-of-the-art of knowledge of the molecular mechanisms by which epithelia and mesenchyme collaborate, and the abnormalities in these mechanisms that may lead to the development of cancer.

Epithelial phenotype is a dynamic stage of differentiation that can be modulated during several physiological or pathological events. The rapid conversion to a mesenchymal-like phenotype is called an epithelial-mesenchymal transition (EMT). The Rise and Fall of Epithelial Phenotype is the first book to comprehensively introduce the concept of EMT. The first part of this volume describes main examples and models and explains their physiological relevance. These examples include hydra morphogenesis, gastrulation in mouse, drosophila and sea urchin, as well as neural crest cell migration and heart morphogenesis in vertebrates. Part two reviews in detail, specific EMT molecular pathways covering extracellular induction, transduction and transcription response and modulation of cell-cell adhesion structures. It emphasizes new specific pathways with potential medical applications. EMTs can also be linked to pathological events such as wound healing and cancer progression, as detailed in this section of the book.