Abstract
One explanation for the clinical association between tumour vascularity and probability of metastasis is that increased primary tumour vascularity enhances haematogenous dissemination by offering greater opportunity for tumour cell invasion into the circulation (intravasation). We devised an experimental tumour metastasis model that allowed manipulation of primary tumour vascularity with differential exposure of the primary and metastatic tumour site to angiogenic agents. We used this model to assess the effects of local and systemic increases in the level of the angiogenic agent basic fibroblast growth factor on metastasis. BDIX rats with implanted hind limb K12/TR adenocarcinoma tumours received either intratumoural or systemic, basic fibroblast growth factor or saline infusion. Both intratumoural and systemic basic fibroblast growth factor infusion resulted in significant increases in tumour vascularity, blood flow and growth, but not lung metastasis, compared with saline-infused controls. Raised basic fibroblast growth factor levels and increase in primary tumour vascularity did not increase metastasis. The clinical association between tumour vascularity and metastasis is most likely to arise from a metastatic tumour genotype that links increased tumour vascularity with greater metastatic potential.
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Acknowledgements
MM Davies was a Stefan Galeski Research Fellow. MM Davies and P Mathur were supported by Colon Cancer Concern, London, UK. The bFGF was supplied by Amgen, California, USA and Bachem, UK. The K12/TR cells were supplied by Dr S Watson, Queens Medical Centre, Nottingham, UK and Dr S Eccles, Institute of Cancer Research, Sutton, UK; and cultured by Dr H Coley and Mr G Box, Institute of Cancer Research, Sutton, UK. We thank Clare Glover MA CStat for statistical advice.
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Davies, M., Mathur, P., Carnochan, P. et al. Effect of manipulation of primary tumour vascularity on metastasis in an adenocarcinoma model. Br J Cancer 86, 123–129 (2002). https://doi.org/10.1038/sj.bjc.6600020
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DOI: https://doi.org/10.1038/sj.bjc.6600020
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