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

Abstract

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.

3D‐electron microscopic characterization of interstitial cells in the human bladder upper lamina propria

“…6. We did not find c-kit + interstitial Cells of Cajal (ICCs) in the ULP as recently reported by our group, 15 but the bIC shared some ultrastructural features with ICCs (partly coverage by basal lamina, small cell body, several thick branching processes with mitochondria localized at the branching points). The bIC in our specimen penetrated the BM of the urothelium and made budding contacts to urothelial cells (Fig.…”

Functional Expression of Transient Receptor Potential and Piezo1 Channels in Cultured Interstitial Cells of Human-Bladder Lamina Propria

“…Several molecular markers are used to characterize bladder ICs: the broad mesenchymal marker vimentin (Vim) ( Davidson and Mccloskey, 2005 ; Gevaert et al, 2014 ), the myogenic differentiation marker alpha-smooth muscle actin ( Monaghan et al, 2012 ; Neuhaus et al, 2018 ) (α-SMA), platelet-derived growth factor receptor alpha (PDGFRα) ( Monaghan et al, 2012 ; Gevaert et al, 2014 ) and the protooncogene c-Kit ( Mccloskey and Gurney, 2002 ). It should be noted that c-Kit, the assumed specific marker for interstitial cells of Cajal (ICC), recently has been found to be expressed only on mast cells in urinary bladder ( Gevaert et al, 2017 ). Upper lamina propria in the human bladder are characterized as Vim + /αSMA + /PDGFRα + /c-kit-.…”

Mechanosensitivity Is a Characteristic Feature of Cultured Suburothelial Interstitial Cells of the Human Bladder

“…The major differences in their distribution define sublayers of the lamina propria, referred to as the upper lamina propria and deeper lamina propria [8]. Recent comparative studies on ICs in human and the major laboratory animals suggest that the understanding of the roles of ICs partly needs revision [7,9,10].…”