Syndecan-1 and Heparanase: Potential Markers for Activity Evaluation and Differential Diagnosis of Crohn's Disease
INFLAMMATORY BOWEL DISEASES
Authors: Zhang, Shaoheng; Qing, Qing; Wang, Qunying; Xu, Jun; Zhi, Fachao; Park, Pyong W.; Zhang, Yali; Chen, Ye
Abstract
Background: Syndecan-1 (SDC1) and its endo-beta-D-glucuronidase heparanase (HPA) are implicated in the maintenance of intestinal barrier function, but their detailed functions in Crohn's disease (CD) are not fully investigated. The aim of this study was to determine alteration patterns of SDC1 and HPA and their potential roles in evaluating disease activity and differentiating CD from intestinal tuberculosis (ITB). Methods: Tissue and serum specimens were obtained from 89 patients, including 15 patients with functional bowel disorders, 18 active patients with ITB, and 56 patients with CD (remission = 19, active = 37). Basic clinical data were collected and routine blood tests were analyzed. SDC1 and HPA were measured by immunohistochemistry, enzyme-linked immunosorbent assay, reverse transcriptase polymerase chain reaction, and western blot. Colonic epithelial cells were incubated with recombinant HPA, tumor necrosis factor alpha (TNF-alpha), and mycobacterium tuberculosis culture filtrate protein to detect the alterations of SDC1 and HPA. Results: In the CD group, SDC1 was significantly decreased in mucosa and increased in serum, whereas HPA level in both were elevated. Such alterations were associated with clinicopathological features representing disease activity and injury severity and were not available in functional bowel disorder and ITB groups. Recombinant HPA incubation increased soluble SDC1 in culture supernatants (P = 2 x 10(-4)), and low-dose TNF-alpha effectively enhanced HPA's activity (P = 3 x 10(-6)). Exogenous TNF-alpha destroyed cellular SDC1 and raised HPA expressions dose dependently, whereas mycobacterium tuberculosis culture filtrate protein showed no effects. Conclusions: Unique alterations of SDC1 and HPA are shown in both patients with CD and in vitro model. The results indicate SDC1 and HPA are potential markers for CD in evaluating its disease activity and differentiating it from ITB.
A subset of high Gleason grade prostate carcinomas contain a large burden of prostate cancer syndecan-1 positive stromal cells
PROSTATE
Authors: Sharpe, Benjamin; Alghezi, Dhafer A.; Cattermole, Claire; Beresford, Mark; Bowen, Rebecca; Mitchard, John; Chalmers, Andrew D.
Abstract
BackgroundThere is a pressing need to identify prognostic and predictive biomarkers for prostate cancer to aid treatment decisions in both early and advanced disease settings. Syndecan-1, a heparan sulfate proteoglycan, has been previously identified as a potential prognostic biomarker by multiple studies at the tissue and serum level. However, other studies have questioned its utility. MethodsAnti-Syndecan-1 immunohistochemistry was carried out on 157 prostate tissue samples (including cancerous, adjacent normal tissue, and non-diseased prostate) from three independent cohorts of patients. A population of Syndecan-1 positive stromal cells was identified and the number and morphological parameters of these cells quantified. The identity of the Syndecan-1-positive stromal cells was assessed by multiplex immunofluorescence using a range of common cell lineage markers. Finally, the burden of Syndecan-1 positive stromal cells was tested for association with clinical parameters. ResultsWe identified a previously unreported cell type which is marked by Syndecan-1 expression and is found in the stroma of prostate tumors and adjacent normal tissue but not in non-diseased prostate. We call these cells Prostate Cancer Syndecan-1 Positive (PCSP) cells. Immunofluorescence analysis revealed that the PCSP cell population did not co-stain with markers of common prostate epithelial, stromal, or immune cell populations. However, morphological analysis revealed that PCSP cells are often elongated and displayed prominent lamellipodia, suggesting they are an unidentified migratory cell population. Analysis of clinical parameters showed that PCSP cells were found with a frequency of 20-35% of all tumors evaluated, but were not present in non-diseased normal tissue. Interestingly, a subset of primary Gleason 5 prostate tumors had a high burden of PCSP cells. ConclusionsThe current study identifies PCSP cells as a novel, potentially migratory cell type, which is marked by Syndecan-1 expression and is found in the stroma of prostate carcinomas, adjacent normal tissue, but not in non-diseased prostate. A subset of poor prognosis high Gleason grade 5 tumors had a particularly high PCSP cell burden, suggesting an association between this unidentified cell type and tumor aggressiveness.