Epithelial metaplasia: adult stem cell reprogramming and (pre)neoplastic transformation mediated by inflammation?

Abstract

Throughout adult life, new developmental commitment of adult stem cells causes metaplastic conversions to occur frequently in some organs. These reversible epithelial replacements are almost always observed in association with chronic inflammation and persistent irritation. Although metaplasia is not synonymous with dysplasia, clinical surveillance has demonstrated that these adaptive processes have an increased susceptibility to evolve into cancer. We propose that cytokines and other soluble factors released by both epithelial and inflammatory cells might alter the transcription-factor expression profile of stem cells and lead to the development of metaplasia. Furthermore, inflammatory mediators might also promote the malignant transformation of epithelial metaplasia by inducing genetic and epigenetic changes and by preventing the immune system from mounting an efficient anti-tumour immune response. A better understanding of the molecular mechanisms leading to metaplasia might help in the design of new therapies for neoplastic and degenerative diseases.