L-Iduronate-Rich Glycosaminoglycans Inhibit Growth of Normal Fibroblasts Independently of Serum or Added Growth Factors

Westergren‐Thorsson, Gunilla; Persson, Sylvi; Isaksson, Anders; Onnervik, Per-Ola; Malmström, Anders; Fransson, Lars‐Âke

doi:10.1006/excr.1993.1124

Cited by 44 publications

(31 citation statements)

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“…As shown in Figure 2 previously [21]. Polyamine-biosynthesis inhibition with DFMO resulted in reduced growth (45 % of control).…”

Section: Hs and Xyl-pheno 2 Inhibit Proliferation Of Fibroblasts Madementioning

confidence: 67%

“…HS is also involved in the internalization of viruses [18], and it has been reported that gene complexes, consisting of polycations and DNA, enter cells via binding to membrane-associated HSPG [19,20]. Moreover, exogenously added GAGs, such as dermatan sulphate (DS) and highly-sulphated HS, inhibit growth of fibroblasts by an unknown mechanism [21]. Human fibroblasts produce PGs that predominantly contain two classes of GAG : DS, chondroitin sulphate (CS) or HS.…”

Section: Introductionmentioning

confidence: 99%

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Proteoglycan involvement in polyamine uptake

Belting

Persson

Fransson

1999

Biochemical Journal

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We have evaluated the possible role of proteoglycans in the uptake of spermine by human lung fibroblasts. Exogenous glycosaminoglycans behaved as competitive inhibitors of spermine uptake, the most efficient being heparan sulphate (K i l 0.16p0.04 µM). Treatment of fibroblasts with either heparan sulphate lyase, p-nitrophenyl-O-β--xylopyranoside or chlorate reduced spermine uptake considerably, whereas chondroitin sulphate lyase had a limited effect. Inhibition of polyamine biosynthesis with α-difluoromethylornithine resulted in an increase of cell-associated heparan sulphate proteoglycans exhibiting higher affinity for spermine. The data indicate a specific role for heparan sulphate proteoglycans in the uptake of spermine by fibroblasts. Spermine uptake by pgsD-677, a mutant Chinese hamster ovary cell defective in heparan sulphate biosynthesis, was only moderately reduced (20 %) compared with wild-type

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“…As shown in Figure 2 previously [21]. Polyamine-biosynthesis inhibition with DFMO resulted in reduced growth (45 % of control).…”

Section: Hs and Xyl-pheno 2 Inhibit Proliferation Of Fibroblasts Madementioning

confidence: 67%

Section: Introductionmentioning

confidence: 99%

Proteoglycan involvement in polyamine uptake

Belting

Persson

Fransson

1999

Biochemical Journal

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“…For example, HS fragments generated after heparinase I treatment or heparinase III treatment of tumor cells have been shown to either promote or inhibit tumor growth in vivo, depending on their composition (25). Similarly, treatment of melanoma cells with chondroitinase AC or chondroitinase B has been reported to inhibit growth and migration in vitro (26), and other studies have showed inhibition as well as promotion of cell growth by HS and CS/DS (27)(28)(29). Here, we demonstrated that the CS/DS was responsible for the cytotoxic effect of the XylNapOHprimed GAGs from HCC70 cells, whereas the XylNapOHprimed HS did not have any effect on cell growth.…”

Section: Discussionmentioning

confidence: 99%

Xyloside-primed Chondroitin Sulfate/Dermatan Sulfate from Breast Carcinoma Cells with a Defined Disaccharide Composition Has Cytotoxic Effects in Vitro

Persson

Tykesson

Westergren‐Thorsson

et al. 2016

Journal of Biological Chemistry

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We previously reported that the xyloside 2-(6-hydroxynaphthyl) ␤-D-xylopyranoside (XylNapOH), in contrast to 2-naphthyl ␤-D-xylopyranoside (XylNap), specifically reduces tumor growth both in vitro and in vivo. Although there are indications that this could be mediated by the xyloside-primed glycosaminoglycans (GAGs) and that these differ in composition depending on xyloside and cell type, detailed knowledge regarding a structure-function relationship is lacking. In this study we isolated XylNapOH-and XylNap-primed GAGs from a breast carcinoma cell line, HCC70, and a breast fibroblast cell line, CCD-1095Sk, and demonstrated that both XylNapOH-and XylNap-primed chondroitin sulfate/dermatan sulfate GAGs derived from HCC70 cells had a cytotoxic effect on HCC70 cells and CCD-1095Sk cells. The cytotoxic effect appeared to be mediated by induction of apoptosis and was inhibited in a concentration-dependent manner by the XylNap-primed heparan sulfate GAGs. In contrast, neither the chondroitin sulfate/ dermatan sulfate nor the heparan sulfate derived from CCD1095Sk cells primed on XylNapOH or XylNap had any effect on the growth of HCC70 cells or CCD-105Sk cells. These observations were related to the disaccharide composition of the XylNapOH-and XylNap-primed GAGs, which differed between the two cell lines but was similar when the GAGs were derived from the same cell line. To our knowledge this is the first report on cytotoxic effects mediated by chondroitin sulfate/dermatan sulfate.

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“…In tumor, different changes of PGs composition and structure occur-expression of PG genes, type, number and size of GAG chains, degree and patterns of sulfation and epimerization of GAGs. 1,2 Other changes apart, a change of epimerization of GAG chains seems to be very important for the antimitotic activity of different PGs: the antiproliferative activity of dermatan sulfate (DS) in human lung fibroblasts increased with increasing iduronate content 3 ; in the presence of serum mitogens or different growth factors, L-iduronate (IdoA)-rich GAGs inhibited proliferation of normal fibroblasts cells 4 ; Liduronic acid (IdoA)-rich heparin (He) and heparan sulfates (HS) had significant antiproliferative effects on mesothelioma cells, while GlcA-rich HS had no significant effects 5 ; chondroitin sulfate (CS), DS and especially He strongly inhibited cell proliferation of both normal osteoblasts and transformed osteoblastic cells mainly because of the presence of large amounts of IdoA-derived trisulfated disaccharides. 6 In tumors, significant increased amount of GlcUA-containing GAGs and decreased amount of IdoUA has been reported for decorin and versican in human rectum carcinoma.…”

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confidence: 99%

Decreased expression of human D‐glucuronyl C5‐epimerase in breast cancer

Grigorieva¹,

Eshchenko²,

Рыкова³

et al. 2007

Intl Journal of Cancer

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D-glucuronyl C5-epimerase (GLCE) is one of the key enzymes in proteoglycan biosynthesis. However, nothing is known about expression and activity of the protein in cancer. In this study, we investigated GLCE expression in human breast cancer using multipex RT-PCR, QRT-PCR and Western-blot assays. In total, 21 patients without malignancy and 74 patients with breast tumor were investigated. The obtained data showed that in 82-84% of human breast tumors there is either downregulation or loss of Dglucuronyl C5-epimerase mRNA expression and significant decrease of the protein content. In most cases (77%), GLCE expression was decreased also in the normal-appearing tissue surrounding the tumor node but the protein amount was comparable to normal breast tissue. These findings represent the first data about involvement of human D-glucuronyl C5-epimerase in malignant transformation. ' 2007 Wiley-Liss, Inc.

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L-Iduronate-Rich Glycosaminoglycans Inhibit Growth of Normal Fibroblasts Independently of Serum or Added Growth Factors

Cited by 44 publications

References 0 publications

Proteoglycan involvement in polyamine uptake

Proteoglycan involvement in polyamine uptake

Xyloside-primed Chondroitin Sulfate/Dermatan Sulfate from Breast Carcinoma Cells with a Defined Disaccharide Composition Has Cytotoxic Effects in Vitro

Decreased expression of human D‐glucuronyl C5‐epimerase in breast cancer

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