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Cellular basis of urothelial squamous metaplasia
: roles of lineage heterogeneity and cell replacement
2 Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016
3 Department of Urology, New York University School of Medicine, New York, NY 10016
4 Department of Microbiology, New York University School of Medicine, New York, NY 10016
5 Department of Pharmacology, New York University School of Medicine, New York, NY 10016
6 New York University Cancer Institute, New York University School of Medicine, New York, NY 10016
7 Institute of Cell Biology, University of Ljubljana Medical Faculty, Lipiceva 2, Ljubljana 1105, Slovenia
Correspondence to Tung-Tien Sun: Sunt01{at}med.nyu.edu
Although the epithelial lining of much of the mammalian urinary tract is known simply as the urothelium, this epithelium can be divided into at least three lineages of renal pelvis/ureter, bladder/trigone, and proximal urethra based on their embryonic origin, uroplakin content, keratin expression pattern, in vitro growth potential, and propensity to keratinize during vitamin A deficiency. Moreover, these cells remain phenotypically distinct even after they have been serially passaged under identical culture conditions, thus ruling out local mesenchymal influence as the sole cause of their in vivo differences. During vitamin A deficiency, mouse urothelium form multiple keratinized foci in proximal urethra probably originating from scattered K14-positive basal cells, and the keratinized epithelium expands horizontally to replace the surrounding normal urothelium. These data suggest that the urothelium consists of multiple cell lineages, that trigone urothelium is closely related to the urothelium covering the rest of the bladder, and that lineage heterogeneity coupled with cell migration/replacement form the cellular basis for urothelial squamous metaplasia.
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