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Circulating levels of angiogenesis-related growth factors in breast cancer: a study to profile proteins responsible for tubule formation.

Barron, Gemma A.; Goua, Marie; Wahle, Klaus W.J.; Bermano, Giovanna


Marie Goua

Klaus W.J. Wahle


The present study exploited a versatile in vitro endothelial cell/fibroblast co-culture cell system to investigate the association between angiogenesis and breast cancer by comparing the capacity of plasma from women with breast cancer and age-matched controls, to influence tubule formation and modulate angiogenesis in vitro, and to identify plasma circulating factors which might be responsible. Plasma from women with breast cancer (n=8) (added on day 7 after co-culture establishment) significantly increased tubule formation by 57% (P < 0.01) when compared to cultures grown in culture medium lacking in vascular endothelial growth factor (VEGF) and fetal bovine serum (FBS), whereas plasma from controls (n=8) did not. Higher levels of VEGF, tumour necrosis factor-alpha (TNF alpha) and interleukin (IL)-6, but not leptin, were observed in plasma samples of the breast cancer group compared to the control group (n=20 in each group). In independent experiments, the effects of VEGF, TNF alpha, IL-6 and leptin were assessed, and it was found that tubule formation was differentially affected whether these inflammatory cytokines or adipokines were added individually or in combination to the co-culture system. Using Proteome Profiler human angiogenesis array kits, 12 out of 55 angiogenesis-related proteins were differentially expressed in plasma from the breast cancer group compared to the control group. Pro-angiogenic proteins included: amphiregulin, artemin, coagulation factor III, fibroblast growth factor (FGF) acidic, GDNF, IL-8, macrophage inflammatory protein (MIP)-1 alpha, platelet derived growth factor-AB/platelet derived growth factor-BB (PDGF-AB/PDGF-BB) and VEGF, whereas anti-angiogenic proteins were: angiopoietin-2, serpin F1 and serpin B5. In addition, FGF acidic was further identified as differentially expressed, with increased expression, when plasma samples from the normal and cancer groups, which induced an increase in tubule formation, were compared to one another. In conclusion, the present study identified angiogenesis-related proteins circulating in the serum of women with breast cancer that are likely to facilitate the growth and metastasis of breast cancer, in part through their influence on tubule formation, and, therefore, may be potential targets for new cancer therapies.


BARRON, G.A., GOUA, M., WAHLE, K.W.J. and BERMANO, G. 2017. Circulating levels of angiogenesis-related growth factors in breast cancer: a study to profile proteins responsible for tubule formation. Oncology reports [online], 38(3), pages 1886-1894. Available from:

Journal Article Type Article
Acceptance Date Jun 15, 2017
Online Publication Date Jul 11, 2017
Publication Date Sep 30, 2017
Deposit Date Aug 21, 2017
Publicly Available Date Jan 12, 2018
Journal Oncology reports
Print ISSN 1021-335X
Electronic ISSN 1791-2431
Publisher Spandidos Publications
Peer Reviewed Peer Reviewed
Volume 38
Issue 3
Pages 1886-1894
Keywords Angiogenesis; Breast cancer; Coculture; Cytokines
Public URL


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