The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Bagheri‐Yarmand, Rozita; Kourbali, Yamina; Mabilat, Christelle; Morère, J. F.; Martin, Antoine; Lű, He; Soria, Claudine; Jozefonvicz, J.; Crépin, Michel

doi:10.1038/bjc.1998.451

Cited by 23 publications

(17 citation statements)

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“…The A431 growth decrease by CMDB7 in vitro could involve the inhibition of other mitogenic growth factors. This interpretation can be strengthened by our previous studies demonstrating that CMDB7 inhibited the activity of heparin-binding PDGF and TGFb by altering their conformation, but did not change the activity of EGF and IGF1, which are not heparin-binding growth factors (Bagheri-Yarmand et al, 1997, 1998a. Independently, the possible VEGF autocrine pathway in A431 could mediate tumour cell survival by protecting them from apoptosis as it was recently reported for breast cancer MDA-MB-231 cells (Bachelder et al, 2001).…”

Section: Discussionmentioning

confidence: 65%

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

et al. 2003

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Vascular endothelial growth factor (VEGF) expression is elevated in a wide variety of solid tumours. Inhibition of VEGF activities is able to reduce angiogenesis and tumour growth. We have recently shown in vitro that carboxymethyl dextran benzylamide (CMDB7) prevents the binding of VEGF 165 to its cell surface receptors and thus inhibits VEGF activities on endothelial cells. In the present study, we explored the effects of CMDB7 on highly aggressive human epidermoid carcinoma A431 cells known to overexpress epidermal growth factor receptors (EGFRs) and produce a high amount of VEGF and a minor quantity of bFGF. In vitro, CMDB7 blocked the mitogenic activity of A431-conditioned medium on endothelial cells. Concerning A431 cells, CMDB7 inhibited their proliferation and the VEGF 165 binding to them. In vivo, administration of CMDB7 (10 mg kg À1 ) three times per week for 2 weeks inhibited the growth of A431 xenografts in nude mice by 73% as compared to the control group. Immunostaining of endothelial cells with mouse-specific GSL-1 lectin in tumour sections revealed that CMDB7 also inhibited the density of intratumour endothelial cells by 66%. These findings demonstrate that CMDB7 has an efficient antiangiogenic and antitumour action in vivo even when tumour cells produce a high level of VEGF and EGFRs.

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Section: Discussionmentioning

confidence: 65%

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

et al. 2003

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“…The control group received s.c. 0.1 ml of NaCl 0.9%. A tumour volume was calculated as previously described (Bagheri-Yarmand et al, 1998a).…”

Section: Xenografts In Nude Micementioning

confidence: 99%

“…Previous reports indicated that MCF-7ras cells secreted the growth factors mitogenic for BALBc/3T3 fibroblasts (Bagheri-Yarmand et al, 1998a). We investigated whether CMDB LS4 or NaPa could influence the mitogenic activity of MCF-7ras cell conditionned medium (CM) ( Figure 5).…”

Section: Effect Of Napa and Cmdb Ls4 On Mcf-7 Ras CM Mitogenic Activimentioning

confidence: 99%

“…We recently showed that carboxymethyl benzylamide dextran derivative (in particular CMDB7) inhibits the breast cancer cell proliferation in vitro and in nude mice (Bagheri-Yarmand et al, 1992, 1998a, b, 1999. This effect in vitro is associated with a decrease in the S-phase cell population and with an accumulation of cells in G1 phase of cell cycle (Bagheri-Yarmand et al, 1992).…”

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“…CMDB7 disrupts the mitogenic effect of growth factors by preventing their binding to specific receptors as reported for Fibroblast Growth Factor-2 and -4 (FGF2, FGF4, BagheriYarmand et al, 1998a), Platelet-Derived Growth Factor-BB and Transforming Growth Factor-β1 (PDGF-BB, TGFΒ BagheriYarmand et al, 1998b). In vivo, CMDB7 treatment reduces the growth of MCF-7ras (Bagheri-Yarmand et al, 1998b) and FGF4-transfected HBL100 xenografts and decreases the tumour angiogenesis (Bagheri-Yarmand et al, 1998a).…”

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Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

et al. 2001

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Summary Sodium phenylacetate (NaPa) and carboxymethyl benzylamide dextran derivative (CMDB LS4 ) are able to inhibit growth of breast tumour cells. In this study, we explored whether the combination of NaPa and CMDB LS4 may enhance their respective inhibitory effects on the MCF-7ras cell growth in vitro and in vivo. NaPa inhibited MCF-7ras cell proliferation by reducing the DNA replication concomitantly with a recruitment of cells in G0/G1 phase and by inducing apoptosis in a dose-and time-dependent manner. The addition of CMDB LS4 potentiated the NaPa antiproliferative effect in the manner dependent on the ratio of CMDB LS4 and NaPa concentrations. In nude mice, CMDB LS4 (150 mg kg -1 ) or NaPa (40 mg kg -1 ) administrated twice a week, for 7 weeks inhibited MCF-7ras xenograft growth by 40% and 60%, respectively. The treatment by both, CMDB LS4 and NaPa, decreased tumour growth by 83% without any toxicity. To better understand the mechanism of NaPa and CMDB LS4 action we assessed their effect on mitogenic activity of MCF-7ras conditioned medium (CM) on BALBC/3T3 fibroblasts. CMDB LS4 added to the CM, inhibited its mitogenic activity whereas NaPa had an anti-mitogenic effect when CM was prepared from MCF-7ras cells pretreated with NaPa. Thus, the antiproliferative effects of NaPa and CMDB LS4 involve 2 different mechanisms explaining, at least in part, the possible synergism between them. Overall, this study points to the potential use of a combination of dextran derivatives with NaPa to inhibit the breast tumour growth.

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Carboxymethyl benzylamide sulfonate dextrans (CMDBS), a family of biospecific polymers endowed with numerous biological properties: A review

Logeart-Avramoglou

Jozefonvicz

1999

J. Biomed. Mater. Res.

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The functionalized dextrans termed carboxymethyl benzylamide sulfonate dextran (CMDBS) represent a family encompassing a wide range of polymers. These soluble macromolecular compounds, which are substituted with specific chemical functional groups, are designed to interact with living systems. By analogy with glycosaminoglycan heparin, a natural highly charged anionic polysaccharide that exerts a variety of biological effects, we postulated that CMDBS compounds also possess binding sites capable of specific interactions with biological constituents, depending on the overall composition of the polymer. The synthesis and heparin-like properties of these CMDBS have been extensively investigated. Thus, it appears that dextran derivatives can mimic the action of heparin in regard to its interactions with antithrombin and serine proteases involved in blood coagulation. Other derivatives interact with various components of the immune system or with adhesive proteins such as fibronectin in modulating the proliferation of Staphylococcus aureus. Because they are able to stimulate wound healing in various in vivo models, these polysaccharides may also constitute a family of tissue repair agents because of their protecting and potentiating effects with heparin binding growth factors. Moreover, dextran derivatives in contact with cells such as endothelial cells, smooth muscle cells, or tumoral cells can affect both cell proliferation and metabolism. It appears that these bioactive polymers are also efficient tools to investigate the precise mechanism of action of individual biological activities by contrasting their mode of action to that of heparin. In addition to their numerous biological properties and biospecificity, functionalized dextrans are relatively simple to manufacture and exempt of donor contaminant, which make them attractive in a variety of clinical applications.

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The suppression of fibroblast growth factor 2/fibroblast growth factor 4-dependent tumour angiogenesis and growth by the anti-growth factor activity of dextran derivative (CMDB7)

Cited by 23 publications

References 23 publications

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

Carboxymethyl benzylamide dextran inhibits angiogenesis and growth of VEGF-overexpressing human epidermoid carcinoma xenograft in nude mice

Sodium phenylacetate enhances the inhibitory effect of dextran derivative on breast cancer cell growth in vitro and in nude mice

Carboxymethyl benzylamide sulfonate dextrans (CMDBS), a family of biospecific polymers endowed with numerous biological properties: A review

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