Microenvironmental regulation of stem cells in intestinal homeostasis and cancer

  • Medema J
  • Vermeulen L
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Abstract

The identification of intestinal stem cells as well as their malignant counterparts, colon cancer stem cells, has undergone rapid development in recent years. Under physiological conditions, intestinal homeostasis is a carefully balanced and efficient interplay between stem cells, their progeny and the microenvironment. These interactions regulate the astonishingly rapid renewal of the intestinal epithelial layer, which consequently puts us at serious risk of developing cancer. Here we highlight the microenvironment-derived signals that regulate stem-cell fate and epithelial differentiation. As our understanding of normal intestinal crypt homeostasis grows, these developments may point towards new insights into the origin of cancer and the maintenance and regulation of cancer stem cells. T he astounding renewal capacity of the intestinal epithelium 1 has made the intestine one of the favourite tissues in which to study stem-cell regulation. The fact that almost all epithelial cells in the intestinal lining are replaced on a weekly basis puts great demands on the cellular organization of this tissue, and also puts it at serious risk of malignant conversion. Indeed, colorectal cancer (CRC) is one of the most common human cancers worldwide, with approximately 1.2 million new cases every year 2

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Authors

  • Jan Paul Medema

  • Louis Vermeulen

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