The stem cell growth factor receptor KIT is not expressed on interstitial cells in bladder

The mast/stem cell growth factor receptor KIT has long been assumed to be a specific marker for interstitial cells of Cajal (ICC) in the bladder, with possible druggable perspectives. However, several authors have challenged the presence of KIT+ ICC in recent years. The aim of this study was therefore to attempt to clarify the conflicting reports on KIT expression in the bladder of human beings, rat, mouse and guinea pig and to elucidate the possible role of antibody‐related issues and interspecies differences in this matter. Fresh samples were obtained from human, rat, mouse and guinea pig cystectomies and processed for single/double immunohistochemistry/immunofluorescence. Specific antibodies against KIT, mast cell tryptase (MCT), anoctamin‐1 (ANO1) and vimentin were used to characterize the cell types expressing KIT. Gut (jejunum) tissue was used as an external antibody control. Our results revealed KIT expression on mast cells but not on ICC in human, rat, mouse and guinea pig bladder. Parallel immunohistochemistry showed KIT expression on ICC in human, rat, mouse and guinea pig gut, which confirmed the selectivity of the KIT antibody clones. In conclusion, we have shown that KIT+ cells in human, rat, mouse and guinea pig bladder are mast cells and not ICC. The present report is important as it opposes the idea that KIT+ ICC are present in bladder. In this perspective, functional concepts of KIT+ ICC being involved in sensory and/or motor aspects of bladder physiology should be revised.

[1]  E. Torlakovic,et al.  Getting controls under control: the time is now for immunohistochemistry , 2015, Journal of Clinical Pathology.

[2]  E. Vanstreels,et al.  Identification of different phenotypes of interstitial cells in the upper and deep lamina propria of the human bladder dome. , 2014, The Journal of urology.

[3]  M. Vannucchi,et al.  Telocytes subtypes in human urinary bladder , 2014, Journal of cellular and molecular medicine.

[4]  M. Mikov,et al.  C-KIT signaling in cancer treatment. , 2014, Current pharmaceutical design.

[5]  T. Roskams,et al.  Administration of imatinib mesylate in rats impairs the neonatal development of intramuscular interstitial cells in bladder and results in altered contractile properties , 2014, Neurourology and urodynamics.

[6]  J. Huizinga,et al.  Interstitial Cells of Cajal: Update on Basic and Clinical Science , 2014, Current Gastroenterology Reports.

[7]  K. Andersson,et al.  Lamina propria: The functional center of the bladder? , 2014, Neurourology and urodynamics.

[8]  M. Zeidel,et al.  Cellular Expression Profile for Interstitial Cells of Cajal in Bladder - A Cell Often Misidentified as Myocyte or Myofibroblast , 2012, PloS one.

[9]  T. Roskams,et al.  Identification of telocytes in the upper lamina propria of the human urinary tract , 2012, Journal of cellular and molecular medicine.

[10]  K. McCloskey,et al.  Identification of PDGFRα positive populations of interstitial cells in human and guinea pig bladders. , 2012, The Journal of urology.

[11]  S. Ward,et al.  Platelet-derived growth factor receptor-α cells in mouse urinary bladder: a new class of interstitial cells , 2012, Journal of cellular and molecular medicine.

[12]  T. Roskams,et al.  Characterization of upper lamina propria interstitial cells in bladders from patients with neurogenic detrusor overactivity and bladder pain syndrome , 2011, Journal of cellular and molecular medicine.

[13]  Kwangsung Park,et al.  Distribution of interstitial cells of cajal and expression of nitric oxide synthase after experimental bladder outlet obstruction in a rat model of bladder overactivity , 2011, Neurourology and urodynamics.

[14]  R. M. Cunningham,et al.  Morphological Expression of KIT Positive Interstitial Cells of Cajal in Human Bladder , 2010, The Journal of urology.

[15]  R. West,et al.  Ano1 is a selective marker of interstitial cells of Cajal in the human and mouse gastrointestinal tract. , 2009, American journal of physiology. Gastrointestinal and liver physiology.

[16]  F. Smedts,et al.  Ultrastructure of Cajal-like interstitial cells in the human detrusor , 2009, Cell and Tissue Research.

[17]  Y. Kojima,et al.  Altered distribution of interstitial cells in the guinea pig bladder following bladder outlet obstruction. , 2008, Neurourology and urodynamics.

[18]  J. Huizinga,et al.  Interstitial cells of Cajal in health and disease. Part I: Normal ICC structure and function with associated motility disorders , 2007, Histopathology.

[19]  S. Biers,et al.  The functional effects of a c‐kit tyrosine inhibitor on guinea‐pig and human detrusor , 2006, BJU international.

[20]  M. Faussone-Pellegrini,et al.  Relationships between neurokinin receptor-expressing interstitial cells of Cajal and tachykininergic nerves in the gut , 2006, Journal of cellular and molecular medicine.

[21]  J. Vente,et al.  Expression of neuronal nitric oxide synthase (nNOS) and nitric-oxide-induced changes in cGMP in the urothelial layer of the guinea pig bladder , 2005, Cell and Tissue Research.

[22]  K. McCloskey,et al.  Morphology and localization of interstitial cells in the guinea pig bladder: structural relationships with smooth muscle and neurons. , 2005, The Journal of urology.

[23]  Y. Kitamura,et al.  Kit as a human oncogenic tyrosine kinase. , 2004, Cellular and molecular life sciences : CMLS.

[24]  Y. Kitamura,et al.  Oncogenic protein tyrosine kinases , 2004, Cellular and Molecular Life Sciences CMLS.

[25]  A. Shafik,et al.  Identification of interstitial cells of Cajal in human urinary bladder: concept of vesical pacemaker. , 2004, Urology.

[26]  T. Roskams,et al.  Identification of kit positive cells in the human urinary tract. , 2004, The Journal of urology.

[27]  D. Fabbro,et al.  Imatinib: a selective tyrosine kinase inhibitor. , 2002, European journal of cancer.

[28]  C. Fry,et al.  Gap junctions and connexin expression in human suburothelial interstitial cells , 2002, BJU International.

[29]  A. Gurney,et al.  Kit positive cells in the guinea pig bladder. , 2001, The Journal of urology.

[30]  S. Nishikawa,et al.  Requirement of c-kit for development of intestinal pacemaker system. , 1992, Development.