Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line

Damiens, Eve; Yazidi, Ikram El; Mazurier, Joël; Elass, Elisabeth; Duthille, Isabelle; Spik, Geneviève; Boilly-Marer, Y.

doi:10.1016/s0171-9335(98)80093-9

Cited by 64 publications

(51 citation statements)

References 26 publications

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“…Interaction was efficiently reduced following heparinase treatment, thus confirming that both cell lines are appropriate cellular models to analyze the interaction between CyPB and cell surface HS. Epithelia cell lines express high levels of membrane-associated HS, which have been reported to support interactions with various extracellular ligands (43,44). However, we found here that HeLa, MCF7, T-47D, and MDA-MB-231 epithelia cells were unable to specifically interact with immobilized CyPB.…”

Section: Cypb Binding To Hs/heparin Is Dependent On N-sulfatecontrasting

confidence: 65%

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Synthesis of Heparan Sulfate with Cyclophilin B-binding Properties Is Determined by Cell Type-specific Expression of Sulfotransferases

Deligny

Denys

Marcant

et al. 2010

Journal of Biological Chemistry

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Cyclophilin B (CyPB) induces migration and adhesion of T lymphocytes via a mechanism that requires interaction with 3-O-sulfated heparan sulfate (HS). HS biosynthesis is a complex process with many sulfotransferases involved. N-Deacetylases/ N-sulfotransferases are responsible for N-sulfation, which is essential for subsequent modification steps, whereas 3-O-sulfotransferases (3-OSTs) catalyze the least abundant modification. These enzymes are represented by several isoforms, which differ in term of distribution pattern, suggesting their involvement in making tissue-specific HS. To elucidate how the specificity of CyPB binding is determined, we explored the relationships between the expression of these sulfotransferases and the generation of HS motifs with CyPB-binding properties. We demonstrated that high N-sulfate density and the presence of 2-O-and 3-O-sulfates determine binding of CyPB, as evidenced by competitive experiments with heparin derivatives, soluble HS, and anti-HS antibodies. We then showed that target cells, i.e. CD4 ؉ lymphocyte subsets, monocytes/macrophages, and related cell lines, specifically expressed high levels of NDST2 and 3-OST3 isoforms. Silencing the expression of NDST1, NDST2, 2-OST, and 3-OST3 by RNA interference efficiently decreased binding and activity of CyPB, thus confirming their involvement in the biosynthesis of binding sequences for CyPB. Moreover, we demonstrated that NDST1 was able to partially sulfate exogenous substrate in the absence of NDST2 but not vice versa, suggesting that both isoenzymes do not have redundant activities but do have rather complementary activities in making N-sulfated sequences with CyPB-binding properties. Altogether, these results suggest a regulatory mechanism in which cell type-specific expression of certain HS sulfotransferases determines the specific binding of CyPB to target cells.Initially identified as cyclosporin A-binding proteins, cyclophilins are peptidyl-prolyl cis-trans isomerases involved in various biological processes, including protein folding, mitochondrial functions, apoptosis, and regulation of trafficking and signaling (1, 2). Besides the repertoire of intracellular functions in which they have been implicated, secreted cyclophilins A and B (CyPB) 2 were reported to be mediators of inflammation and innate immunity. They trigger chemotaxis of neutrophils, T lymphocytes, and monocytes/macrophages by way of interactions with CD147 and cell surface heparan sulfate (HS) (3-7). CyPB also induces integrin-mediated adhesion of CD4 ϩ T lymphocytes and monocytes/macrophages to fibronectin, by a mechanism that requires interaction with the HS moieties of syndecan-1 and association of CD147 with CD98, the latter being an activator of ␤1 integrins (4,8,9).HS consists of alternating N-acetyl/N-sulfate glucosamine (GlcNAc/GlcNS) and GlcUA/IdoUA residues clustered in a series of domains of relatively high IdoUA content and sulfate density (NS domains), bound by short transition zones with intermediate sulfation patterns and separated by N-a...

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Section: Cypb Binding To Hs/heparin Is Dependent On N-sulfatecontrasting

confidence: 65%

“…Data are representative of three independent experiments. sequence of interaction with N-sulfate groups in NS domains of HS (43,44). We therefore used this protein as a model of HSbinding ligand in the following experiments.…”

Section: Silencing the Expression Of Hs Sulfotransferases Efficientlymentioning

confidence: 99%

Synthesis of Heparan Sulfate with Cyclophilin B-binding Properties Is Determined by Cell Type-specific Expression of Sulfotransferases

Deligny

Denys

Marcant

et al. 2010

Journal of Biological Chemistry

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“…Another possible difference may be that a certain period of time is necessary for LF to activate the immune system. LF has been demonstrated to enhance cytotoxic activities of monocytes [2,25] and NK cells [6,7,36,37]. To evaluate augmentation of the immune system by LF, another in vivo experiment should be carried out by using older but susceptible mice, or by quantitative virus detection assay.…”

Section: Discussionmentioning

confidence: 99%

Characterization of in vitro and in vivo Antiviral Activity of Lactoferrin and Ribavirin upon Hantavirus.

Murphy

Kariwa

Mizutani

et al. 2001

The Journal of Veterinary Medical Science

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ABSTRACT. Mechanisms of anti-hantaviral activities of bovine lactoferrin (LF) and ribavirin (Rbv) were investigated. Hantavirus focus formation at 48 hr was 15% of the control in cells treated with 400 µg/ml LF for 1 hr at 37°C prior to viral infection. Post infection treatment with 100 µg/ml Rbv also inhibited the focus formation to 2.5% of the control. Combined LF pre-and Rbv post-infection treatment completely inhibited focus formation. Viral glycoprotein (G2) and nucleocapsid protein (NP) syntheses were delayed in LF pretreated cells up to 24 hr post infection (hpi) but became comparable to the control by 48 hpi. Further, LF inhibited viral shedding at 24 hpi but did not inhibit shedding after 48 hpi. However, Rbv was able to inhibit synthesis of viral proteins, (+) and (-) strand RNAs also inhibited viral shedding after 24 hr. These results suggest that LF inhibits viral adsorption to cells, while Rbv inhibits viral RNA synthesis. For in vivo trials of LF and Rbv, LF pre-and Rbv post-treatment were evaluated in suckling mice infected with hantavirus, of which 7% survived. LF concentrations of 40 and 160 mg/kg administered prior to viral challenge improved survival rates to 15% and 70%, respectively for single administration and 85% and 94%, respectively, for double administration. Rbv concentrations of 25 and 50 mg/kg gave survival rates of 68% and 81%, respectively. This suggests that both LF and Rbv are efficacious in hantavirus infection in vivo.

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“…Lactoferrin binds to cells by at least two mechanisms: 1) high capacity low-affinity binding that may occur via charge-charge interactions with surface glycolipids or other molecules such as DNA (71)(72)(73)(74)(75)(76) and 2) lower capacity/higher affinity binding to one or more proteinaceous plasma membrane receptors (77)(78)(79)(80)(81)(82)(83). Lactoferrin has been reported to bind to B cells via interaction with DNA on the cell surface (74,75) and it appears that B cell binding is mediated through the highly charged N-terminal sequence of lactoferrin (84).…”

Section: Discussionmentioning

confidence: 99%

Lactoferrin Binds CpG-Containing Oligonucleotides and Inhibits Their Immunostimulatory Effects on Human B Cells

Britigan

Lewis

Waldschmidt³

et al. 2001

The Journal of Immunology

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Unmethylated CpG dinucleotide motifs in bacterial DNA, as well as oligodeoxynucleotides (ODN) containing these motifs, are potent stimuli for many host immunological responses. These CpG motifs may enhance host responses to bacterial infection and are being examined as immune activators for therapeutic applications in cancer, allergy/asthma, and infectious diseases. However, little attention has been given to processes that down-modulate this response. The iron-binding protein lactoferrin is present at mucosal surfaces and at sites of infection. Since lactoferrin is known to bind DNA, we tested the hypothesis that lactoferrin will bind CpG-containing ODN and modulate their biological activity. Physiological concentrations of lactoferrin (regardless of iron content) rapidly bound CpG ODN. The related iron-binding protein transferrin lacked this capacity. ODN binding by lactoferrin did not require the presence of CpG motifs and was calcium independent. The process was inhibited by high salt, and the highly cationic N-terminal sequence of lactoferrin (lactoferricin B) was equivalent to lactoferrin in its ODN-binding ability, suggesting that ODN binding by lactoferrin occurs via charge-charge interaction. Heparin and bacterial LPS, known to bind to the lactoferricin component of lactoferrin, also inhibited ODN binding. Lactoferrin and lactoferricin B, but not transferrin, inhibited CpG ODN stimulation of CD86 expression in the human Ramos B cell line and decreased cellular uptake of ODN, a process required for CpG bioactivity. Lactoferrin binding of CpG-containing ODN may serve to modulate and terminate host response to these potent immunostimulatory molecules at mucosal surfaces and sites of bacterial infection.

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Role of heparan sulphate proteoglycans in the regulation of human lactoferrin binding and activity in the MDA-MB-231 breast cancer cell line

Cited by 64 publications

References 26 publications

Synthesis of Heparan Sulfate with Cyclophilin B-binding Properties Is Determined by Cell Type-specific Expression of Sulfotransferases

Synthesis of Heparan Sulfate with Cyclophilin B-binding Properties Is Determined by Cell Type-specific Expression of Sulfotransferases

Characterization of in vitro and in vivo Antiviral Activity of Lactoferrin and Ribavirin upon Hantavirus.

Lactoferrin Binds CpG-Containing Oligonucleotides and Inhibits Their Immunostimulatory Effects on Human B Cells

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