Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer

Szarvas, Tibor; Sevcenco, Sabina; Módos, Orsolya; Keresztes, Dávid; Nyírády, Péter; Kubik, András; Romics, Miklós; Kovalszky, Ilona; Reis, Henning; Hadaschik, Boris; Shariat, Shahrokh F.; Kramer, Gero

doi:10.1016/j.urolonc.2018.03.010

Cited by 23 publications

(16 citation statements)

References 31 publications

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“…Studies in multiple myeloma and breast and colon cancer detected specific proteases, including MMP-7, which is synthetized by the tumor cells, and is able to proteolytically remove the ectodomain of SDC1 [ 21 ]. In accordance, we previously found in two independent patient cohorts of bladder and prostate cancer that high soluble serum SDC1 levels are directly associated with elevated MMP-7 serum levels [ 14 , 17 ], which suggests MMP-7 as a major protease for SDC1 shedding. In the present study, we also detected a positive correlation between serum SDC1 and previously measured MMP-7 levels in BC, which further confirmed the role of MMP-7 in SDC1 shedding.…”

Section: Discussionsupporting

confidence: 89%

“…Further studies reported that SDC1 shedding is enhanced as a response to chemotherapy and shed SDC1 was found to be associated with chemotherapy resistance in colorectal cancer [ 16 ]. Similarly, we demonstrated high circulating pre-treatment SDC1 levels to be independently associated with poor response to docetaxel chemotherapy in patients with castration-resistant prostate cancer [ 17 ]. Our present analyses revealed for the first time an independent association between high baseline serum SDC1 concentrations and shorter OS in platinum-treated BC patients.…”

Section: Discussionmentioning

confidence: 99%

“…Matrix metalloproteinase-7 (MMP-7) is one of the few molecules capable of shedding the SDC1 ectodomain region [ 16 ]. Additional data suggested the involvement of SDC1 in the resistance to systemic treatments of various malignancies [ 16 , 17 , 18 ].…”

Section: Introductionmentioning

confidence: 99%

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Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients

et al. 2020

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Cisplatin-containing chemotherapy represents the first-line treatment for patients with locally advanced or metastatic muscle-invasive bladder cancer. Recently, novel therapies have become available for cisplatin-ineligible or -resistant patients. Therefore, prediction of cisplatin response is required to optimize therapy decisions. Syndecan-1 (SDC1) tissue expression and serum concentration may be associated with cisplatin resistance. Thus, pre-treatment serum levels of SDC1 and its expression in chemo-naïve tissues were assessed in 121 muscle-invasive bladder cancer patients who underwent postoperative platinum-based chemotherapy. SDC1 concentrations were evaluated by ELISA in 52 baseline and 90 follow-up serum samples and tissue expressions were analyzed by immunohistochemistry in an independent cohort of 69 formalin-fixed paraffin-embedded tumor samples. Pre-treatment SDC1 serum levels were significantly higher in lymph node metastatic (p = 0.009) and female patients (p = 0.026). SDC1 tissue expression did not correlate with clinicopathological parameters. High pre-treatment SDC1 serum level and the presence of distant metastasis were independent risk factors for overall survival (Hazard ratio (HR): 1.439, 95% Confidence interval (CI): 1.003–2.065, p = 0.048; HR: 2.269, 95%CI: 1.053–4.887, p = 0.036). Our results demonstrate an independent association between high baseline serum SDC1 concentration and poor survival in platinum-treated patients. Analyzing baseline serum SDC1 levels may help to predict platinum-containing chemotherapy and could help to optimize therapeutic decision-making.

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Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

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Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients

et al. 2020

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“…To be more specific, PGs conferred resistance to tumor therapy by activating key signals such as activation of EGFR-AKT signaling by versican, inducing breast cancer self-renewal [ 256 ] and chemotherapy resistance [ 49 ], activating NF-κB signaling by biglycan to promote resistance to chemotherapy of colon cancer [ 43 ] and activating the EGFR pathway by syndecan-1 to lead to chemoresistance in colon cancer [ 257 ]. Circulating syndecan-1 contributed to chemotherapy resistance in prostate cancer [ 114 ]. For a more detailed presentation about the targeting of these molecules and the corresponding curative effect, the reader can read the recent comprehensive work presented in Reference [ 258 ].…”

Section: Clinical Featuresmentioning

confidence: 99%

Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression

Wei

Huang

et al. 2020

IJMS

110

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The extracellular matrix (ECM) spatiotemporally controls cell fate; however, dysregulation of ECM remodeling can lead to tumorigenesis and cancer development by providing favorable conditions for tumor cells. Proteoglycans (PGs) and glycosaminoglycans (GAGs) are the major macromolecules composing ECM. They influence both cell behavior and matrix properties through direct and indirect interactions with various cytokines, growth factors, cell surface receptors, adhesion molecules, enzymes, and glycoproteins within the ECM. The classical features of PGs/GAGs play well-known roles in cancer angiogenesis, proliferation, invasion, and metastasis. Several lines of evidence suggest that PGs/GAGs critically affect broader aspects in cancer initiation and the progression process, including regulation of cell metabolism, serving as a sensor of ECM’s mechanical properties, affecting immune supervision, and participating in therapeutic resistance to various forms of treatment. These functions may be implemented through the characteristics of PGs/GAGs as molecular bridges linking ECM and cells in cell-specific and context-specific manners within the tumor microenvironment (TME). In this review, we intend to present a comprehensive illustration of the ways in which PGs/GAGs participate in and regulate several aspects of tumorigenesis; we put forward a perspective regarding their effects as biomarkers or targets for diagnoses and therapeutic interventions.

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“…However, in different types of cancers, syndecan-1 and syndecan-4 may present the opposite effect, promoting the tumor progression [ 64 , 65 ]. In addition, it has already been demonstrated that the shed of syndecan-1 is associated with chemotherapy resistance in castration-resistant prostate cancer [ 66 ]. These data evidence that the function of cell surface HSPGs can be altered by extracellular ectodomain shedding by proteases, converting them into soluble paracrine effector molecules.…”

Section: Heparan Sulfate Proteoglycansmentioning

confidence: 99%

Heparan Sulfate Proteoglycans in Human Colorectal Cancer

Vicente

Silva

Sartorio

et al. 2018

Analytical Cellular Pathology

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Colorectal cancer is the third most common cancer worldwide, accounting for more than 610,000 mortalities every year. Prognosis of patients is highly dependent on the disease stage at diagnosis. Therefore, it is crucial to investigate molecules involved in colorectal cancer tumorigenesis, with possible use as tumor markers. Heparan sulfate proteoglycans are complex molecules present in the cell membrane and extracellular matrix, which play vital roles in cell adhesion, migration, proliferation, and signaling pathways. In colorectal cancer, the cell surface proteoglycan syndecan-2 is upregulated and increases cell migration. Moreover, expression of syndecan-1 and syndecan-4, generally antitumor molecules, is reduced. Levels of glypicans and perlecan are also altered in colorectal cancer; however, their role in tumor progression is not fully understood. In addition, studies have reported increased heparan sulfate remodeling enzymes, as the endosulfatases. Therefore, heparan sulfate proteoglycans are candidate molecules to clarify colorectal cancer tumorigenesis, as well as important targets to therapy and diagnosis.

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Circulating syndecan-1 is associated with chemotherapy-resistance in castration-resistant prostate cancer

Cited by 23 publications

References 31 publications

Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients

Soluble Syndecan-1 Levels Are Associated with Survival in Platinum-Treated Bladder Cancer Patients

Roles of Proteoglycans and Glycosaminoglycans in Cancer Development and Progression

Heparan Sulfate Proteoglycans in Human Colorectal Cancer

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