FGF-2 Dimerization Involvement in Growth Factor Mediated Cell Proliferation but Not Cell Differentiation

Berghe, L. Van Den; Mortier, I; Zanibellato, Catherine; Amalríc, François; Piégay, Hervé; Bugler, Béatrix

doi:10.1006/bbrc.1998.9668

Cited by 9 publications

(5 citation statements)

References 42 publications

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“…26 As a possible explanation, Ward et al 37 demonstrate that IL-6 M is more potent than IL-6 D in a STAT3 phosphorylation assay, suggesting that both IL-6 forms mediate different intracellular signals. Moreover, Van den Berghe et al 47 have found recently that although monomers and dimers of the fibroblast growth factor-2 (FGF-2), another well-known dimeric soluble factor, show similar receptor binding capacity, their biologic capacities are different. Interestingly, monomeric FGF-2 induced cell differentiation but not cell proliferation.…”

Section: Discussionmentioning

confidence: 99%

Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells

Moreno

Villar

Cámara

et al. 2001

Blood

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Tumoral lymphocytes from patients with Bchronic lymphocytic leukemia (B-CLL) are long-lived cells in vivo, but they die rapidly by apoptosis in vitro. Here, it is reported that endothelial cells (ECs) inhibit the apoptosis of B-CLL cells, as determined by 4 different flow cytometric methods, and that this antiapoptotic effect is mediated mainly by soluble factor(s), as can be deduced from the following findings. First, EC-conditioned medium (ECCM) inhibited the apoptotic rate in B-CLL to approximately 50% of control. Second, the antiapoptotic effect mediated by EC/B-CLL cell contact was more apparent than real; using a fluorescence-based phagocytosis assay, it was demonstrated that this effect was due to the phagocytic capacity of ECs, which internalized apoptotic cells. Third, the protective effect of ECCM was associated neither with proliferation nor differentiation signals. Fourth, the survival factor was a dimeric form of IL-6 because anti-IL-6 antibodies completely neutralized the antiapoptotic effect mediated not only by the crude ECCM but also by the 45-to 55-kd active fractions obtained after gel filtration, which contained high levels of IL-6. These IL-6 dimers (IL-6 D ) were nonco-

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Section: Discussionmentioning

confidence: 99%

Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells

Moreno

Villar

Cámara

et al. 2001

Blood

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“…This modified procedure overcame the disadvantage of the low digestibility of 6-O-desulfated heparin purified by the previous procedure, resulting in high enzymatic digestibility of the completely 6-Odesulfated heparins that were at the levels similar to that of intact heparin. The MTSTFA-treated 100% 6-O-desulfated heparin with clarified physicochemical properties is a useful tool for the evaluation of the involvement of 6-O-sulfate group(s) of heparin in the interaction between heparin, bFGF, and FGFRs (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29), as well as the present 80 and 90% 6-Odesulfated heparins with reference to intact heparin.…”

Section: -O-desulfated Heparin Enhances Mitogenic Activity Of Bfgfmentioning

confidence: 99%

“…Specific removal of major sulfate groups of heparin such as 2-O-sulfate, 6-Osulfate, and N-sulfate groups would be useful in order to clarify the backbone structures of oligosaccharides bearing specific array of sulfate groups responsible for the interactions with physiologically active molecules. For instance, selective removal of 6-O-sulfate groups from glucosamine residues of heparin is of great importance in order to evaluate the involvement of 6-O-sulfate group(s) in the interaction between heparin, bFGF, and FGF receptors (FGFRs) (13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25)(26)(27)(28)(29).…”

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confidence: 99%

Preparation of Completely 6-O-Desulfated Heparin and Its Ability to Enhance Activity of Basic Fibroblast Growth Factor

Kariya¹,

Kyogashima²,

Suzuki³

et al. 2000

Journal of Biological Chemistry

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Although regioselective removal of 6-O-sulfate groups of heparin has been undertaken by several researchers, complete 6-O-desulfation with little side reaction has not been attained successfully. In this work, a modified method with a certain silylating reagent, N-methyl-N-(trimethylsilyl)trifluoroacetamide, has been established to produce completely 6-O-desulfated heparin with few other chemical changes. The degrees of 6-O-desulfation were estimated by means of chemical disaccharide analyses and/or 13 C NMR spectra. Although the completely 6-O-desulfated heparin lost about 20% of 2-O-sulfate groups, any other chemical changes and depolymerization were not detected. The completely 6-O-desulfated heparin displayed strong inhibition of COS-1 cell adhesion to basic fibroblast growth factor (bFGF)-coated well in a dose-dependent manner, as was clarified by the competitive cell-adhesion assay. Furthermore, the completely 6-O-desulfated heparin was shown to promote in vitro A31 fibroblast proliferation in a dose-dependent manner in the presence of bFGF. These results suggest that signal transduction through bFGF/bFGF receptor in A31 cells occurs in the absence of 6-O-sulfate groups in heparin. The involvement of 6-O-sulfate group(s) of heparin/heparan sulfate in the promotion of bFGF mitogenic activity was reported by several groups. This discrepancy between our results and those of other groups would be due to the differences in molecular size of heparin/heparan sulfate derivatives and/or cell species used for the assay. Heparin and heparan sulfate (HS)1 are known as glycosaminoglycan (GAG) components of extracellular matrix-forming connective tissues of animals. The former GAG, heparin, is exclusively distributed in mast cells, and the latter GAG, HS, is widely distributed in animal tissues. With the accumulation of the information concerning biological roles of heparin and HS, it has been revealed that their biological functions mostly depend upon interaction between polysaccharides and physiologically active molecules, although the biological roles of heparin and HS are highly diverged. For instance, they interact with lipoprotein lipase (1, 2), anti-thrombin III (3, 4), basic fibroblast growth factor (bFGF) (5-8), etc. Furthermore, minimum structures of heparin and/or HS necessary for binding with antithrombin III and/or bFGF have been determined (9, 12). Chemical modification of heparin has been undertaken by several researchers, focusing on the elucidation of the mechanism underlying interaction between heparin and the physiologically active molecules as described above. Specific removal of major sulfate groups of heparin such as 2-O-sulfate, 6-Osulfate, and N-sulfate groups would be useful in order to clarify the backbone structures of oligosaccharides bearing specific array of sulfate groups responsible for the interactions with physiologically active molecules. For instance, selective removal of 6-O-sulfate groups from glucosamine residues of heparin is of great importance in order to evaluate the involvemen...

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“…A similar argument holds for the alternate 1:1:2 model, solved using biophysical analysis (50). While FGF2 dimers are linked to the proliferative signaling complex (104,105), the identification of two receptor binding surfaces on FGF2 (106) presents the possibility that under certain circumstances, FGFR dimerization FIGURE 7 (a) Prediction of the intracellular processing of FGF2 for Model A. Model predictions (dotted line) are compared to experimentally measured results from VSMCs exposed to 0.28 nM FGF2 (76).…”

Section: Relevance Of Other Proliferative Signaling Complex Stoichiommentioning

confidence: 64%

Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

Dupree

Pollack

Levine

et al. 2006

Biophysical Journal

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Fibroblast growth factor 2 (FGF2) can enhance the proliferative capacity of bone and bone marrow stromal cells; however, the mechanisms behind this effect are not well described. We present a whole-cell kinetic model relating receptor-mediated binding, internalization, and processing of FGF2 to osteoblastic proliferative response. Focusing on one of the potential signaling complex stoichiometries, we utilized experimentally measured and modeled estimated rate constants to predict in vitro proliferation and distinguish between potential binding orders. We found that piecewise assemblage of a ternary signaling complex may occur in several ways depending on the local binding environment. Using experimental data of endocytosed FGF2 as a constraint, we have also shown evidence of potential multistep processes involved in heparan-sulfate proteoglycans-bound FGF2 release, internalization, and fragment formation in conjunction with the normal metabolism of the proteoglycan.

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FGF-2 Dimerization Involvement in Growth Factor Mediated Cell Proliferation but Not Cell Differentiation

Cited by 9 publications

References 42 publications

Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells

Interleukin-6 dimers produced by endothelial cells inhibit apoptosis of B-chronic lymphocytic leukemia cells

Preparation of Completely 6-O-Desulfated Heparin and Its Ability to Enhance Activity of Basic Fibroblast Growth Factor

Fibroblast Growth Factor 2 Induced Proliferation in Osteoblasts and Bone Marrow Stromal Cells: A Whole Cell Model

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