Pancreatic carcinoma is characterized by elevated content of hyaluronan and chondroitin sulfate with altered disaccharide composition

Theocharis, Achilleas D.; Tsara, Marina E.; Papageorgacopoulou, N.; Karavias, Dionisios; Theocharis, Dimitrios A.

doi:10.1016/s0925-4439(00)00051-x

Cited by 161 publications

(139 citation statements)

References 23 publications

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“…DDi-0S disaccharide is the predominant disaccharide found in pancreatic carcinoma (10) and is increased 4-fold in gastric carcinoma compared with normal tissue (28). Furthermore, gastric carcinomas exhibit increased DDi-0S and DDi-6S disaccharides with a parallel decrease in DDi-4S disaccharides.…”

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 96%

“…Increased proportions of DDi-0S disaccharides have been observed in laryngeal (26), rectal (19), colon (7), liver (27), pancreatic (10), and head and neck tumor tissues (9) compared with normal tissue. DDi-0S disaccharide is the predominant disaccharide found in pancreatic carcinoma (10) and is increased 4-fold in gastric carcinoma compared with normal tissue (28).…”

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 99%

“…The concentration of chondroitin sulfate is greatly increased over normal tissue levels in several different malignancies (7)(8)(9)(10), including prostate cancer (11)(12)(13). Our previous studies illustrated that patients treated by radical prostatectomy for early stage (cT 1 -cT 2 ) cancer who showed high chondroitin sulfate concentration in the peritumoral stroma of the prostate had a significantly higher incidence of PSA failure than patients with low chondroitin sulfate concentration (14).…”

Section: Introductionmentioning

confidence: 99%

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Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse

Sakko

Butler

Byers

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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The glycosaminoglycan chondroitin sulfate is significantly increased in the peritumoral stroma of prostate tumors compared with normal stroma and is an independent predictor of prostate-specific antigen (PSA) relapse following radical prostatectomy. In this study, we determined whether specific alterations in the sulfation pattern of glycosaminoglycan chains in clinically organ-confined prostate cancer are associated with PSA relapse. Immunoreactivity to distinct glycosaminoglycan disaccharide epitopes was assessed by manually scoring the staining intensity in prostate tissues from patients with benign prostatic hyperplasia (n = 19), early-stage cancer (cohort 1, n = 55 and cohort 2, n = 275), and advanced-stage cancer (n = 20). Alterations to glycosaminoglycans in benign and malignant prostate tissues were determined by cellulose acetate chromatography and high-pressure liquid chromatography. Glycosaminoglycan disaccharide epitopes were localized to the peritumoral stroma of clinically localized prostate cancer. The level of immunostaining for unsulfated disaccharides (C0S) in the peritumoral stroma, but not for 4-sulfated (C4S) or 6-sulfated disaccharides (C6S), was significantly associated with the rate of PSA relapse following radical prostatectomy. High levels of C0S immunostaining were determined to be an independent predictor of PSA relapse (1.6-fold, P = 0.020). Advanced-stage prostate cancer tissues exhibited reduced electrophoretic mobility for chondroitin sulfate and increased unsulfated disaccharides when compared with benign prostatic hyperplasia tissues, whereas the sulfated disaccharide levels were unaffected. The level of C0S immunostaining in the peritumoral stroma is an independent determinant of PSA failure in clinically localized prostate cancer. Specific alterations to chondroitin sulfate side chains occurring during tumor development may be a crucial step for disease progression in prostate cancer. (Cancer Epidemiol Biomarkers Prev 2008;17(9):2488 -97)

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Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 96%

Section: Cancer Epidemiology Biomarkers and Prevention Cancer Epidemiomentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse

Sakko

Butler

Byers

et al. 2008

Cancer Epidemiology, Biomarkers &Amp; Prevention

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“…23 In addition, versican expression has been associated with tumor progression and decreased survival in various tumor types. [24][25][26] In cervical cancer, versican has been suggested to enhance tumor invasion and metastases formation. 20 In this study, we have investigated the presence, isotype and location of versican in cervical carcinoma.…”

mentioning

confidence: 99%

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

et al. 2010

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Cervical carcinoma is the second most frequent cancer type in women worldwide. Both inflammatory cells and stromal cells are important for tumor progression. Stromal cells produce growth factors and extracellular matrix and provide an adequate environment for angiogenesis. Versican, a member of the extracellular matrix, has been shown to have a role in tumor progression. The aim of this study was to investigate versican expression, and its association with tumor-infiltrating inflammatory cell subsets and with clinicopathological parameters in human cervical cancers. We have studied the expression of versican in 149 cervical cancers using immunohistochemistry and mRNA in situ hybridization. Versican was predominantly expressed in the stroma (myofibroblasts). Using quantitative real-time-PCR, V0 was found to be the most prominent isoform. High stromal versican expression was significantly associated with a low number of tumor-infiltrating T cells (P ¼ 0.018) and particularly a low number of CD8-positive T cells (cytotoxic T cells; P ¼ 0.002). Stromal versican expression was significantly higher in patients with an infiltration depth 414 mm (P ¼ 0.004) and in patients with parametrial invasion (P ¼ 0.044). Stromal versican expression was not associated with survival. Our results suggest that versican expression in the stromal compartment of cervical cancers results in reduced numbers of intraepithelial CD8-positive T cells and enhanced local invasion.

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“…26 Changes in ECM hyaluronan levels are known to occur in pancreatitis 27 and in pancreatic cancer. 28 Hyaluronan in the ECM provides a favorable microenvironment for cell proliferation and migration by maintaining the turgidity and hydration of tissue, in addition to activating intracellular signals through interaction with cell surface receptors. Increased expression of hyaluronan is sufficient to induce epithelial-mesenchymal transition and acquisition of transformed properties in phenotypically normal epithelial cell receptors.…”

Section: Organization Of the Ecm In The Pancreasmentioning

confidence: 99%

Visualization of Mouse Pancreas Architecture Using MR Microscopy

Grippo

Venkatasubramanian

Knop

et al. 2011

The American Journal of Pathology

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Pancreatic diseases, which include diabetes, pancreatitis, and pancreatic cancer, are often difficult to detect and/or stage, contributing to a reduced quality of life and lifespan for patients. Thus, there is need for a technology that can visualize tissue changes in the pancreas, improve understanding of disease progression, and facilitate earlier detection in the human population. Because of low spatial resolution, current clinical magnetic resonance imaging (MRI) at low field strength has yet to fully visualize the exocrine, endocrine, vascular, and stromal components of the pancreas. We used high field strength magnetic resonance microscopy ( MRI) to image mouse pancreas ex vivo without contrast agents at high spatial resolution. We analyzed the resulting high-resolution images using volume rendering to resolve components in the pancreas, including acini, islets, blood vessels, and extracellular matrix. Locations and dimensions of pancreatic components as seen in three-dimensional MRI were compared with histological images, and good correspondence was found. Future longitudinal studies could expand on the use of in vivo MRI in mouse models of pancreatic diseases. Capturing three-dimensional structural changes through MRI could help to identify early cellular and tissue changes associated with pancreatic disease, serving as a mode of improved detection in the clinic for endocrine and exocrine pathologies.

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Pancreatic carcinoma is characterized by elevated content of hyaluronan and chondroitin sulfate with altered disaccharide composition

Cited by 161 publications

References 23 publications

Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse

Immunohistochemical Level of Unsulfated Chondroitin Disaccharides in the Cancer Stroma Is an Independent Predictor of Prostate Cancer Relapse

Versican expression is associated with tumor-infiltrating CD8-positive T cells and infiltration depth in cervical cancer

Visualization of Mouse Pancreas Architecture Using MR Microscopy

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