Heparan Sulfate Proteoglycans in Human Colorectal Cancer

Vicente, Carolina Meloni; Silva, Daiana Aparecida da; Sartorio, Priscila Veronica; Silva, Tiago Donizetti; Saad, Sarhan Sydney; Nader, Helena B.; Forones, Nora Manoukian; Toma, Leny

doi:10.1155/2018/8389595

Cited by 30 publications

(20 citation statements)

References 91 publications

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“…Elevated levels of SDC-4 in breast cancer are correlated to ERs and PgR expression. SDC-4 promotes cell adhesion and inhibits the cellular invasion into collagen as well [ [79] , [80] , [81] , [82] , [83] ]. Heparanase is a matrix degradation enzyme that is involved in the shedding of SDCs.…”

Section: Resultsmentioning

confidence: 99%

Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells

Tavianatou

Piperigkou

Barbera

et al. 2019

Matrix Biology Plus

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High levels of hyaluronan (ΗΑ), a major extracellular matrix (ECM) glycosaminoglycan, have been correlated with poor clinical outcome in several malignancies, including breast cancer. The high and low molecular weight HΑ forms exert diverse biological functions. Depending on their molecular size, ΗΑ forms either promote or attenuate signaling cascades that regulate cancer progression. In order to evaluate the effects of different ΗΑ forms on breast cancer cells' behavior, ΗΑ fragments of defined molecular size were synthesized. Breast cancer cells of different estrogen receptor (ER) status – the low metastatic, ERα-positive MCF-7 epithelial cells and the highly aggressive, ERβ-positive MDA-MB-231 mesenchymal cells – were evaluated following treatment with HA fragments. Scanning electron microscopy revealed that HA fragments critically affect the morphology of breast cancer cells in a molecular-size dependent mode. Moreover, the ΗΑ fragments affect cell functional properties, the expression of major ECM mediators and epithelial-to-mesenchymal transition (ΕΜΤ) markers. Notably, treatment with 200 kDa ΗΑ increased the expression levels of the epithelial marker Ε-cadherin and reduced the expression levels of HA synthase 2 and mesenchymal markers, like fibronectin and snail2/slug. These novel data suggest that the effects of HA in breast cancer cells depend on the molecular size and the ER status. An in-depth understanding on the mechanistic basis of these effects may contribute on the development of novel therapeutic strategies for the pharmacological targeting of aggressive breast cancer.

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Section: Resultsmentioning

confidence: 99%

Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells

Tavianatou

Piperigkou

Barbera

et al. 2019

Matrix Biology Plus

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“…Such discrepant results underline that tumor cells may largely differ from each other and thus also in their reactions to any compounds. Heparan sulfate is described as a proliferation modulating substance and plays an important role in cancer diseases [64,65]. Saad et al showed a decrease in cell viability of hepatocellular cell lines Hep G2 and HuH7 incubated with a mutant glypican 3 (heparan sulfate proteoglycan) without its GPI anchor [66].…”

Section: Discussionmentioning

confidence: 99%

Comparison of the Effects of Fucoidans on the Cell Viability of Tumor and Non-Tumor Cell Lines

et al. 2019

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Fucoidans extracted from brown algae exert manifold biological activities paving the way for the development of numerous applications including treatments outside tumor therapy such as age-related macular degeneration or tissue engineering. In this study, we investigated the antiproliferative effects of fucoidans extracted from six different algae (Fucus vesiculosus, F. serratus, F. distichus subsp. evanescens, Dictyosiphon foeniculaceus, Laminaria digitata, Saccharina latissima) as well as three reference compounds (Sigma fucoidan, heparin, enoxaparin) on tumor (HL-60, Raji, HeLa, OMM-1, A-375, HCT-116, Hep G2) and non-tumor (ARPE-19, HaCaT) cell lines. All fucoidans were extracted according to a standardized procedure and tested in a commercially available MTS assay. Cell viability was measured after 24 h incubation with test compounds (1–100 µg/mL). Apart from few exceptions, fucoidans and heparins did not impair cell viability. In contrast, fucoidans significantly increased cell viability of suspension cell lines, but not of adherent cells. Fucoidans slightly increased viability of tumor cells and had no impact on the viability of non-tumor cells. The cell viability of HeLa and ARPE-19 cells negatively correlated with protein content and total phenolic content (TPC) of fucoidans, respectively. In summary, none of the tested fucoidans turned out to be anti-proliferative, rendering them interesting for future studies and applications.

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“…As shown in Figure 2 D, Lum gene expression was barely detectable by RT-PCR and equal in all MC38 clones. In both Mock- and Snail-MC38 clones, we also analyzed gene expression of other proteoglycans that are known to impact cancer progression [ 37 ]. Gpc1 and syndecan-4 ( Sdc4 ) were the two proteoglycans with the most elevated gene expression in MC38 cells, but the overexpression of Snail did not exert any effect ( Figure 2 D).…”

Section: Resultsmentioning

confidence: 99%

Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail

Papiewska-Pająk

Krzyżanowski

Katela

et al. 2020

Cells

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The transcription factor Snail triggers epithelial-to-mesenchymal transition (EMT), endowing cancer cells with invasive properties during tumor progression. Extracellular vesicles (EVs) released from cancer cells at various stages of cancer progression are known to influence the tumor pre-metastatic niche and metastatic potential. The aim of this study was to analyze the effect of Snail on murine colon adenocarcinoma cells (MC38 line) and on the characteristics of their EVs. Stable clones of Snail-overexpressing MC38 cells were investigated in vitro versus Mock cells. Increased expression of matrix metalloproteinase MMP-14 and augmented activity of MMP-9 and -14 were observed in Snail-MC38 cells. There was no change in the transcriptomic profile of proteoglycans in Snail-MC38 cells; however, the protein level of Glypican-1 (GPC1) was enhanced in EVs released from those cells. Our finding that GPC1 protein level was enhanced in EVs released from MC38 cells that overexpressed Snail and were in an early EMT stage might explain the specificity of the GPC1 biomarker in colon cancer diagnosis. Further, our data suggest that Snail, by changing the level of GPC1 on EVs released by colon cancer cells, may affect the generation of a distant premetastatic niche and metastatic organotropism in colon adenocarcinoma.

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Heparan Sulfate Proteoglycans in Human Colorectal Cancer

Cited by 30 publications

References 91 publications

Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells

Molecular size-dependent specificity of hyaluronan on functional properties, morphology and matrix composition of mammary cancer cells

Comparison of the Effects of Fucoidans on the Cell Viability of Tumor and Non-Tumor Cell Lines

Glypican-1 Level Is Elevated in Extracellular Vesicles Released from MC38 Colon Adenocarcinoma Cells Overexpressing Snail

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