The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function

Sinderen, Michelle Van; Cuman, Carly; Winship, Amy; Menkhorst, Ellen

doi:10.1016/j.placenta.2013.07.065

Cited by 26 publications

(36 citation statements)

References 46 publications

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“…The CSPG component of the placenta has been associated with the ability of the placental cells to maintain high proliferation rates and the capacity of the villous trophoblasts to invade into uterine tissue during implantation (Baston-Büst et al, 2010; Van Sinderen et al, 2013). Invasion and enhanced proliferation are phenotypes shared with cancer cells.…”

Section: Resultsmentioning

confidence: 99%

“…Placental cells, human melanoma cells, and some breast cancer and glioma cells have been found to express high levels of the CSA-modified proteoglycan, CSPG4 (Van Sinderen et al, 2013; Wang et al, 2010). To test whether CSPG4 carries pl-CS that can be bound by rVAR2, we analyzed co-localization and direct interaction between rVAR2 and CSPG4 on C32 melanoma cells.…”

Section: Resultsmentioning

confidence: 99%

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Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

et al. 2015

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SUMMARY Plasmodium falciparum engineer infected erythrocytes to present the malarial protein, VAR2CSA, which binds a distinct type chondroitin sulfate (CS) exclusively expressed in the placenta. Here, we show that the same CS modification is present on a high proportion of malignant cells and that it can be specifically targeted by recombinant VAR2CSA (rVAR2). In tumors, placental-like CS chains are linked to a limited repertoire of cancer-associated proteoglycans including CD44 and CSPG4. The rVAR2 protein localizes to tumors in vivo and rVAR2 fused to diphtheria toxin or conjugated to hemiasterlin compounds strongly inhibits in vivo tumor cell growth and metastasis. Our data demonstrate how an evolutionarily refined parasite-derived protein can be exploited to target a common, but complex, malignancy-associated glycosaminoglycan modification.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

et al. 2015

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“…Delivery was performed using Invitrogen Lipofectamine RNAiMAX Transfection Reagent (Thermo Fisher Scientific, Inc.) according to manufacturer's instructions. Cells were transfected for 72 h prior to RNA collection to test for transfection efficiency or prior to beginning the functional experiments, as described previously (18).…”

Section: Small Interfering Rna (Sirna) Transfection Of Ishikawa Cellsmentioning

confidence: 99%

“…Cells were seeded into the upper chamber at 10,000/well in 5% FCS DMEM medium, and 10% FCS DMEM medium was added to the lower chamber. The CIM-plate 16 was monitored every 30 min for 72 h total (18). Data was calculated using RTCA software version 1.2, supplied with the instrument (ACEA Biosciences, Inc.), and exported for statistical analysis.…”

Section: Small Interfering Rna (Sirna) Transfection Of Ishikawa Cellsmentioning

confidence: 99%

Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation

et al. 2016

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Abstract. Endometrial cancer is the most common invasive gynaecological malignancy. While endocrine, genetic and inflammatory factors are thought to contribute to its pathogenesis, its precise etiology and molecular regulators remain poorly understood. Fibulin-5 is an extracellular matrix (ECM) protein that inhibits cell growth and invasion in several cancer cell types and is downregulated in a number of types of human cancer. However, it is unknown whether fibulin-5 plays a role in endometrial tumourigenesis. In the current report, the expression and localisation of fibulin-5 in type I endometrioid human endometrial cancers of grades (G) 1-3 was investigated using reverse transcription-quantitative polymerase chain reaction and immunohistochemistry. Fibulin-5 mRNA was found to be significantly reduced in whole tumour tissues from women across G1-3 compared with benign endometrium (P<0.0001). Consistently, fibulin-5 protein was also reduced in the tumour epithelial compartment across increasing tumour grades. By contrast, increased protein localisation to the tumour stroma was observed with increasing grade. Knockdown by small interfering RNA in Ishikawa endometrial epithelial cancer cells expressing fibulin-5 stimulated cell adhesion and proliferation in vitro. Fibulin-5 mRNA expression in Ishikawa cells was induced by transforming growth factor-β and fibulin-5 in turn activated extracellular signal-regulated kinases (ERK1/2), suggesting that it may act via the mitogen-activated protein kinase pathway. In summary, the present study identified fibulin-5 as a downregulated ECM gene in human endometrial cancer and observed a shift from epithelial to stromal protein localisation with increasing tumour grade in women.These data suggest that loss of fibulin-5 function may promote endometrial cancer progression by enhancing epithelial cell adhesion and proliferation.

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“…In addition, van Sinderen et al [43] recently analyzed the role of NG2 in the placenta and extravillous trophoblasts. They found that IL-11 and leukemia inhibitory factor (LIF), known to be produced by the placenta in the first trimester [44, 45], stimulate NG2 expression specifically in the placental villi and deciduas.…”

Section: Introductionmentioning

confidence: 99%

The regulatory mechanisms of NG2/CSPG4 expression

et al. 2017

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Neuron-glial antigen 2 (NG2), also known as chondroitin sulphate proteoglycan 4 (CSPG4), is a surface type I transmembrane core proteoglycan that is crucially involved in cell survival, migration and angiogenesis. NG2 is frequently used as a marker for the identification and characterization of certain cell types, but little is known about the mechanisms regulating its expression. In this review, we provide evidence that the regulation of NG2 expression underlies inflammation and hypoxia and is mediated by methyltransferases, transcription factors, including Sp1, paired box (Pax) 3 and Egr-1, and the microRNA miR129-2. These regulatory factors crucially determine NG2-mediated cellular processes such as glial scar formation in the central nervous system (CNS) or tumor growth and metastasis. Therefore, they are potential targets for the establishment of novel NG2-based therapeutic strategies in the treatment of CNS injuries, cancer and other conditions of these types.

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The chrondroitin sulfate proteoglycan (CSPG4) regulates human trophoblast function

Cited by 26 publications

References 46 publications

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Targeting Human Cancer by a Glycosaminoglycan Binding Malaria Protein

Fibulin-5 localisation in human endometrial cancer shifts from epithelial to stromal with increasing tumour grade, and silencing promotes endometrial epithelial cancer cell proliferation

The regulatory mechanisms of NG2/CSPG4 expression

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