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J. Biol. Chem., Vol. 275, Issue 39, 30009-30018, September 29, 2000
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From the To explore how heparan sulfate (HS) controls the
responsiveness of the breast cancer cell lines MCF-7 and MDA-MB-231 to
fibroblast growth factors (FGFs), we have exposed them to HS
preparations known to have specificity for FGF-1 (HS glycosaminoglycan
(HSGAG A)) or FGF-2 (HSGAGB). Proliferation assays confirmed that MCF-7 cells were highly responsive to FGF-2 complexed with GAGB,
whereas migration assays indicated that FGF-1/HSGAGA combinations were stimulatory for the highly invasive MDA-MB-231 cells. Quantitative polymerase chain reaction for the levels of FGF receptor (FGFR) isoforms revealed that MCF-7 cells have greater levels of FGFR1 and
that MDA-MB-231 cells have greater relative levels of FGFR2. Cross-linking demonstrated that FGF-2/HSGAGB primarily activated FGFR1,
which in turn up-regulated the activity of mitogen-activated protein
kinase; in contrast, FGF-1/HSGAGA led to the phosphorylation of equal
proportions of both FGFR1 and FGFR2, which in turn led to the
up-regulation of Src and p125FAK. MDA-MB-231 cells
were particularly responsive to vitronectin substrates in the presence
of FGF-1/HSGAGA, and blocking antibodies established that they used the
The Proliferative and Migratory Activities of Breast Cancer Cells
Can Be Differentially Regulated by Heparan Sulfates*
§,,,, Department of Anatomical Sciences,
University of Queensland, St. Lucia, Queensland 4072, Australia and the
¶ Groupe Facteurs de Croissance, Laboratoire de Biologie du
Developpement (UPRES 1033), Université des Sciences et
Technologies de Lille, 59655 Villeneuve d'Ascq Cedex, France
v
3 integrin to bind to it. These results suggest that the clustering of particular FGFR configurations on breast cancer cells induced by different HS chains leads to distinct
phenotypic behaviors.
*
This work was supported by grants from the Ligue
contre le Cancer, the Région Nord-Pas de Calais, the French
Ministry of Education, the Rhone Poulenc Rohrer Corp., the Traveling
Fellowship of the Australian Academy of Science, and the National
Health and Medical Research Council of Australia.The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement" in accordance with 18 U.S.C. Section
1734 solely to indicate this fact.
Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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