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FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells

Oncogene volume 20, pages 2791–2804 (2001)Cite this article

Abstract

Fibroblast growth factor 8 (FGF-8) is a secreted heparin-binding protein, which has transforming potential. Alternative splicing of the mouse Fgf-8 gene potentially codes for eight protein isoforms (a–h) which differ in their transforming capacity in transfected cells. S115 mouse mammary tumor cells express a transformed phenotype and secrete FGF-8 in an androgen-dependent manner. In order to study the role of FGF-8 isoforms in the induction of transformed phenotype of breast cancer cells, we over-expressed FGF-8 isoforms a, b and e in S115 cells. Over-expression of FGF-8b, but not FGF-8a or FGF-8e, induced androgen and anchorage independent growth of S115 cells. FGF-8b-transfected S115 cells formed rapidly growing tumors with increased vascularization when injected s.c. into nude mice. FGF-8a also slightly increased tumor growth and probably tumor vascularization but FGF-8e was not found to have any effects. The angiogenic activity of FGF-8b and heparin-binding growth factor fraction (HBGF) of S115 cell conditioned media was tested in in vitro and in vivo models for angiogenesis using immortomouse brain capillary endothelial cells (IBEC) and chorion allantoic membrane (CAM) assays. Recombinant FGF-8b protein was able to stimulate proliferation, migration, and vessel-like tube formation of IBECs. In addition, stimulatory effect of S115-HBGF on IBE cell proliferation was evident. A positive angiogenic response to FGF-8b was also seen in CAM assay. The results demonstrate that the expression of Fgf-8b is able to promote vessel formation. Angiogenic capacity probably markedly contributes to the ability of FGF-8b to increase tumor growth of androgen-regulated S115 mouse breast cancer cells.

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Acknowledgements

We thank Dr Olli Lassila and Mrs Heli Niittymäki for help and advice with CAM assays, Prof Kari Alitalo for providing the pLTRpoly and the pSV2-neo expression vectors, Dr Pradip Roy-Burman for providing the FGF-8b-pcDNA3 plasmid and Prof Wallace L McKeehan for FGF-7 cDNA. Prof Lena Claesson-Welsh is gratefully acknowledged for providing us with the IBE cells. Ms Soili Jussila, Mrs Anneli Kurkela, Mrs Pirkko Rauhamäki and Mrs Leena Simola are warmly thanked for excellent technical assistance. This work was supported by grants from the Ida Mountin Foundation, The Finnish Medical Foundation, the Cancer Societies of South-Western Finland, and the Academy of Finland. Johanna Ruohola is a graduate student at the Turku Graduate School in Biomedical Sciences.

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  1. Mirjami MT Mattila and Johanna K Ruohola: MMT Mattila and JK Ruohola contributed equally to this work.

Authors and Affiliations

  1. Department of Anatomy, Institute of Biomedicine, and MediCity Research Laboratory, University of Turku, Turku, 20520, Finland

    Mirjami MT Mattila, Johanna K Ruohola, Eeva M Valve, Merja J Tasanen, Jani A Seppänen & Pirkko L Härkönen

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  1. Mirjami MT Mattila
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  2. Johanna K Ruohola
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Mattila, M., Ruohola, J., Valve, E. et al. FGF-8b increases angiogenic capacity and tumor growth of androgen-regulated S115 breast cancer cells. Oncogene 20, 2791–2804 (2001). https://doi.org/10.1038/sj.onc.1204430

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