Carcinogenic implications of the neighborhood coherence principle (NCP)

A new hypothesis on carcinogenesis is set forth on the basis of the neighborhood coherence principle (NCP). NCP constitutes a general rule of pattern formation and maintenance. According to this principle, a system of interacting cells can produce and maintain a spatial organization by virtue of cell-cell communication. This hypothesis suggests that this homeostasis primarily results from a NCP-like process implying cell-cell communication. Each cell is constrained by its neighbors to maintain the mature phenotype despite its inherent individual variability. If the cell-cell mature communication happens to be impaired, tissue homeostasis is disrupted and a proliferative state can be initiated. A further potential effect may result from the establishment of NCP-like communication specific for proliferative cells allied to paracrine and outocrine factors which can lock the cells into the proliferative mode. Most mechanisms implied in this hypothesis have already been investigated. There is a large body of experimental results supporting the role of junctional communication in cooperative metabolism, growth, differentiation and tumour-related events. This new hypothesis provides a framework within which these known facts may be put in a theoretical perspective; it might well constitute the unifying theory--as yet missing--in carcinogenesis.