TY - JOUR
T1 - Inhibition of MCF-7ras tumor growth by carboxymethyl benzylamide dextran
T2 - Blockage of the paracrine effect and receptor binding of transforming growth factor β1 and platelet-derived growth factor-BB
AU - Bagheri-Yarmand, Rozita
AU - Kourbali, Yamina
AU - Morère, Jean François
AU - Jozefonvicz, Jacqueline
AU - Crépin, Michel
N1 - Copyright:
Copyright 2007 Elsevier B.V., All rights reserved.
PY - 1998
Y1 - 1998
N2 - The highly tumorigenic human breast cancer MDF-7ras line (Ha-ras- transfected MCF-7 cell line) loses estrogen dependence and secretes diffusible growth factors that support its own tumor growth in vivo. Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) inhibits the growth of breast MCF-7 and MCF-7ras cell lines. In this study, we have shown that conditioned medium (CM) from MCF-7 and MCF-7ras cells stimulated the DNA synthesis of BALB/c3T3 fibroblasts and that CMDB7 strongly inhibited these mitogenic effects in a dose-dependent manner. Neutralizing antibodies against platelet-derived growth factor (PDGF) partially inhibited the mitogenic effect of MCF-7ras CM. The flow cytometry analysis of the cell cycle showed that the CM of tumor cells increased the percentage of fibroblasts in S phase and that CMDB7 blocked them in G0/G1 phase. CMDB7 inhibited the mitogenic effect of PDGF-BB and transforming growth factor (TGF) β1 but not those of epidermal growth factors and insulin-like growth factor on BALB/c3T3 fibroblasts. CMDB7 increased the electrophoretic mobility of radiolabeled PDGF-BB and TFG-β1, apparently by forming a stable complex with these factors. On intact BALB/c3T3 fibroblasts, binding of iodinated growth factors (125I-TGF-β1 and 125I-PDGF) to their receptors was completely displaced by CMDB7. In vivo studies demonstrated that s.c. injection of CMDB7 inhibited by 66% the tumor growth of MCF-7ras xenografts in nude mice. These results showed that CMDB7 inhibits the mitogenic effect of growth factors released from MCF-7 and MCF-7ras cells and suppresses tumor growth in the MCF-7ras model.
AB - The highly tumorigenic human breast cancer MDF-7ras line (Ha-ras- transfected MCF-7 cell line) loses estrogen dependence and secretes diffusible growth factors that support its own tumor growth in vivo. Our previous studies showed that carboxymethyl benzylamide dextran (CMDB7) inhibits the growth of breast MCF-7 and MCF-7ras cell lines. In this study, we have shown that conditioned medium (CM) from MCF-7 and MCF-7ras cells stimulated the DNA synthesis of BALB/c3T3 fibroblasts and that CMDB7 strongly inhibited these mitogenic effects in a dose-dependent manner. Neutralizing antibodies against platelet-derived growth factor (PDGF) partially inhibited the mitogenic effect of MCF-7ras CM. The flow cytometry analysis of the cell cycle showed that the CM of tumor cells increased the percentage of fibroblasts in S phase and that CMDB7 blocked them in G0/G1 phase. CMDB7 inhibited the mitogenic effect of PDGF-BB and transforming growth factor (TGF) β1 but not those of epidermal growth factors and insulin-like growth factor on BALB/c3T3 fibroblasts. CMDB7 increased the electrophoretic mobility of radiolabeled PDGF-BB and TFG-β1, apparently by forming a stable complex with these factors. On intact BALB/c3T3 fibroblasts, binding of iodinated growth factors (125I-TGF-β1 and 125I-PDGF) to their receptors was completely displaced by CMDB7. In vivo studies demonstrated that s.c. injection of CMDB7 inhibited by 66% the tumor growth of MCF-7ras xenografts in nude mice. These results showed that CMDB7 inhibits the mitogenic effect of growth factors released from MCF-7 and MCF-7ras cells and suppresses tumor growth in the MCF-7ras model.
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M3 - Article
C2 - 9663468
AN - SCOPUS:0031845838
SN - 1044-9523
VL - 9
SP - 497
EP - 504
JO - Cell Growth and Differentiation
JF - Cell Growth and Differentiation
IS - 6
ER -