Transforming Growth Factor β1 Increases the Synthesis and Shedding of the Melanoma-Specific Proteoglycan in Human Melanoma Cells

Heredia, Ascensión; Villena, Juan; Romaris, Manuel; Molist, Anna; Bassols, Anna

doi:10.1006/abbi.1996.0381

Cited by 8 publications

(11 citation statements)

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“…Conversely, inhibition of C4S and C6S synthesis decreases the expression of these markers and enhances E‐cadherin expression, in agreement with the notion that these markers are increased in clinically relapsing glioblastoma multiforme . TGF ‐β, an inducer of EMT, has been shown to induce CS expression and to bind to CSs, thus contributing to cell migration and invasion . In breast cancer cells, CSs can bind to N‐cadherin, activate the N‐cadherin/β‐catenin pathway, and enhance EMT.…”

Section: Discussionsupporting

confidence: 76%

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

et al. 2019

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Key molecules promoting migration and invasion exist in the extracellular matrix, and include chondroitin 4‐sulfate (C4S) and chondroitin 6‐sulfate (C6S), functionally important carbohydrate chains of chondroitin sulfate proteoglycans that participate in regulating cancer development. Here, we show that C4S and C6S expression is upregulated in human glioma tissues, when compared to normal brain tissue, and that the extent of upregulation positively correlated with glioma malignancy. Treatment of cultured glioma cells with C4S and C6S enhanced cell viability, migration, and invasion, increased MMP‐2 and MMP‐9 levels, enhanced N‐cadherin, but reduced E‐cadherin expression. Inhibition of expression of the two CS synthetic enzymes chondroitin 4‐O‐sulfotransferase‐1 (C4ST‐1/CHST11) and chondroitin 6‐O‐sulfotransferase‐1 (C6ST‐1/CHST3) suppressed cell viability, migration and invasion, reduced MMP‐2 and MMP‐9 expression, and reduced N‐cadherin expression, but increased E‐cadherin levels. The C4S‐ and C6S‐enhanced epithelial‐to‐mesenchymal transition and expression of MMP‐2 occurred via activation of the PI3K/AKT signaling pathway, known to be involved in promoting cell migration and invasion. In immune‐deficient larval zebrafish, C4S and C6S increased the numbers of viable tumor cells, thereby promoting glioma cell proliferation. The present observations point to a novel role of C4S and C6S in human glioma cell functions, thus possibly representing targets in glioma therapy.

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Section: Discussionsupporting

confidence: 76%

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

et al. 2019

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“…Both evidences indicate that this PG is not related to mel-PG. 19 The work presented here identifies this high-molecular weight PG as versican and establishes a close relationship between versican expression and cell differentiation in human melanoma in vitro and in vivo.…”

Section: Discussionmentioning

confidence: 54%

“…17,18 Our group has previously reported an unidentified high-molecular weight PG in undifferentiated human melanoma cell lines. 19 In the present work, we identify this PG as versican and describe its presence in in vivo melanocytic lesions. We also analyze how the various versican isoforms relate to cell differentiation and the role of versican in the biological properties of melanoma cells.…”

mentioning

confidence: 83%

“…This band has been previously identified as the melanoma-specific PG, mel-PG, by immunological methods. 19 All these bands were subsequently identified as chondroitin/dermatan sulfate PGs by digestion with chondroitinase ABC, chondroitinase AC, and heparitinase (not shown). A second group of cell lines produced very small amounts of sulfate-labeled bands (SK-mel-23, DX2, and MeWo).…”

Section: Identification Of Versican In Human Melanoma Cell Linesmentioning

confidence: 99%

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Versican Is Differentially Expressed in Human Melanoma and May Play a Role in Tumor Development

Touab¹,

Villena²,

Barranco

et al. 2002

The American Journal of Pathology

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113

111

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“…In the context of the present investigation, it is of interest that TGF-β has been shown to induce CS in several types of cells, e.g. in mammary epithelial cells (38), melanoma cells (39) and in human lung fibroblasts (40). At a mechanistic level, TGF-β was shown to up-regulate xylosyltransferase-1, i.e.…”

Section: Discussionmentioning

confidence: 83%

Chondroitin sulfate expression predicts poor outcome in breast cancer

et al. 2011

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Abstract. Experimental studies have established that the sulfated glycosaminoglycans heparan sulfate and chondroitin sulfate act as co-receptors of cytokines and growth factors that drive the malignant cell phenotype and the remodelling of the surrounding tumor stroma. However, the clinical relevance of these studies remains ill-defined. The present study investigates the significance of chondroitin sulfate expression in malignant cells and the stroma, respectively, of tumors from two independent cohorts of breast cancer patients (cohort I: 144 patients, 130 evaluable samples; cohort II: 498 patients, 469 evaluable samples; ER-positive patients ~86% in both cohorts). Kaplan-Meier analysis and Cox proportional hazards modelling were used to assess the relationship between chondroitin sulfate and recurrence-free and overall survival. High chondroitin sulfate expression in malignant cells was shown to predict shorter recurrence-free survival (P=0.007, cohort I; P=0.024, cohort II) and overall survival (cohort I: P=0.044; cohort II: P<0.001) in both cohorts. In multivariate analysis, high chondroitin sulfate in malignant cells was shown to be an independent, predictive factor of poor overall survival (cohort I: hazard ratio 2.28: 95% confidence interval 1.08-4.81, P=0.031; cohort II: hazard ratio 1.71: 95% confidence interval 1.23-2.38, P=0.001). However, chondroitin sulfate in the stroma showed no correlation with known markers of tumor aggressiveness or with clinical outcome in either cohort. Our data suggest that high chondroitin sulfate expression in malignant cells is associated with an adverse outcome in patients with primary breast cancer, supporting the idea of a functional and potentially targetable role of chondroitin sulfate in tumor disease.

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Transforming Growth Factor β1 Increases the Synthesis and Shedding of the Melanoma-Specific Proteoglycan in Human Melanoma Cells

Cited by 8 publications

References 0 publications

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

Expression and function of chondroitin 4‐sulfate and chondroitin 6‐sulfate in human glioma

Versican Is Differentially Expressed in Human Melanoma and May Play a Role in Tumor Development

Chondroitin sulfate expression predicts poor outcome in breast cancer

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