Chronic, longstandig inflammation is known to be a hallmark of cancer. Colorectal cancer risk is elevated in longstanding ulcerative colitis (UC). Previously, we found that in active, newly diagnosed UC HGFR+ circulating and subepithelial cells display an expression profile characteristics for mesenchymal-epitehlial transition. The aim of this study was to characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor (HGFR)-expressing cells in longstanding, chronically active UC.
Forty matched peripheral blood and colonic biopsy samples from 20 patients with chronically active UC and 20 healthy controls were collected. After preparing tissue microarrays and blood smears HGFR, CDX2, CD133 and Musashi-1 conventional and double fluorescent immunolabelings were performed, then the samples were digitalized. For semiquantitative counting of immunopositive lamina propria (LP) and blood cells were counted, then mean ± SD were determined. Using laser microdissection subepithelial cells from the lamina propria were collected. Gene expression analysis of HGFR, CD133, CDX2, Lgr5, Musashi-1 and CK20 were performed in all samples by using real-time RT-PCR.
Higher number of HGFR (blood: 7.4 ± 1.3 vs 28.4 ± 2.23; LP: 2.4 ± 0.7 vs 8.15 ± 0.59; P
In chronically active UC, the portion of circulating and subeithelial HGFR-expressing cells decreased, indicating a lower activity of mucosal regeneration by mesenchymal-epithelial transition. However, the higher number of HGFR/CD133 double positive cells may indicate the involvement of CD133 expression in colitis-associated carcinogenesis.
Clinical trial identification
Legal entity responsible for the study
Hungarian Scientific Research Fund (OTKA-K111743 grant)
All authors have declared no conflicts of interest.