Expression and prognostic role of syndecan-2 in prostate cancer

Abstract

Syndecans are a four-member family of transmembrane heparan sulphate proteoglycans that have different functions in cell signalling, adhesion, cytoskeleton organization, migration, proliferation, and angiogenesis. Several studies investigated the role of syndecan-2 (SDC2) in different carcinomas; however, only one being focused on SDC2 in prostate cancer. SDC2 expression and relationship with established prognostic features were assessed in a cohort of 86 patients treated with radical prostatectomy for clinically localized prostate adenocarcinoma. SDC2 expression was present in the majority of prostate cancers and absent in only 11.6% of cases. SDC2 expression was also recorded in cells of prostatic intraepithelial neoplasia, whereas normal prostatic epithelial tissue and stroma did not express SDC2. SDC2 overexpression in prostate cancer was significantly associated with established features indicative of worse prognosis such as higher preoperative PSA (P ¼ 0.011), higher Gleason score (Po0.001), positive surgical margins (Po0.003), and extraprostatic extension of disease (Po0.003). Moreover, expression of SDC2 was also associated with biochemical disease progression on univariate analysis (Po0.001). Study results supported the potential role of SDC2 in prostatic carcinogenesis and cancer progression. Moreover, SDC2 could serve as an additional prognostic marker that might help in further stratifying the risk of disease progression in patients with prostate cancer.

Altered expression patterns of syndecan-1 and -2 predict biochemical recurrence in prostate cancer

“…23 The evidence presented in this work supports the idea that the syndecan-1 serum level may represent a novel clinical marker for prostate cancer. 13,14,18 Unexpectedly, we were not able to find a coordinated downregulation of syndecan-1 membrane expression followed by an upregulation of syndecan-2 membrane expression as part of the epithelial-mesenchymal transition. Nonetheless, we observed increased syndecan-2 cytoplasmic expression in prostate cancer cells, which correlates with a high risk of biochemical recurrence.…”

“…We confirmed that syndecan-1 and, interestingly, syndecan-2, were both expressed in epithelial cells of normal and pathological prostate tissue. Popovic et al 14 have also reported syndecan-2 expression in prostate cancer and prostatic intraepithelial neoplasia samples but not in normal prostate tissue. In our work, we found expression of syndecan-2 at the membranes of basal cells in non-malignant tissue (BPH samples).…”

“…13 Other authors have suggested that syndecan-2 expression could serve as an additional prognostic marker to further stratify the risk of disease progression in patients with prostate cancer. 14 The aim of this study was to use semiquantitative immunohistochemistry to evaluate the expression of syndecan-1 and -2 in prostate cancer samples from patients with clinically localized disease. We also investigated the relationship between syndecan expression and biochemical recurrence (BCR) to assess the potential role of syndecan expression as a predictor of disease relapse after radical prostatectomy.…”

Comparative genome-wide DNA methylation analysis of colorectal tumor and matched normal tissues

“…SDC2 is a cell surface receptor and appears to play diverse and possibly conflicting roles in cancer: SDC2 downregulation was associated with poor prognosis in esophageal squamous cell carcinoma, 36 whereas SDC2 overexpression was associated with poor prognosis in prostate cancer tissue. 37 KCNK12 encodes a member of the potassium channel superfamily, and was shown to be hypermethylated in 32 out of 77 colorectal tumors. 7 Analysis of the DMRs in a large independent cohort of CRC and preferably using an orthogonal analysis method should be performed to evaluate their frequency of hypermethylation in CRC, as well as their clinical value.…”

Shedding; towards a new paradigm of syndecan function in cancer

“…Moreover, colon cancer cells cultured on syndecan-2 ectodomain or syndecan-2 antibody show increased adhesion and spreading (28). Syndecan-2 is also overexpressed in about 90% of prostate cancer patients, and the increased syndecan-2 expression enhances the growth of prostate tumor cells (29). In contrast to other syndecans, which generally function as tumor promoters, syndecan-4 apparently functions as a tumor suppressor.…”