Journal article
Tumor location and nature of lymphatic vessels are key determinants of cancer metastasis
R Shayan, R Inder, T Karnezis, C Caesar, K Paavonen, MW Ashton, GB Mann, GI Taylor, MG Achen, SA Stacker
Clinical and Experimental Metastasis | Published : 2013
Abstract
Tumor metastasis to lymph nodes is a key indicator of patient survival, and is enhanced by the neo-lymphatics induced by tumor-secreted VEGF-C or VEGF-D, acting via VEGFR-3 signalling. These targets constitute important avenues for anti-metastatic treatment. Despite this new understanding, clinical observations linking metastasis with tumor depth or location suggest that lymphangiogenic growth factors are not the sole determinants of metastasis. Here we explored the influence of tumor proximity to lymphatics capable of responding to growth factors on nodal metastasis in a murine VEGF-D over-expression tumor model. We found that primary tumor location profoundly influenced VEGF-D-mediated lym..
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Funding Acknowledgements
The authors thank M. Kesar and staff at the Animal Facility at the Ludwig Institute for Cancer Research, Melbourne, for assistance with mouse experiments; M. Francois for provision of NG2 antibody; J. Taylor for assistance in generating figures; Y. Zhang for histology services; S. Cody for assistance with imaging; and A. Burgess and M. Hibbs for critical reading of this manuscript. Animal experiments and treatment of archived human tissue samples were in accordance with NH&MRC guidelines. This work was funded partly by a Program Grant from the National Health and Medical Research Council of Australia (NH&MRC). SAS and MGA are supported by Senior Research Fellowships from the NH&MRC. SAS would like to acknowledge the support of the Pfizer Australia Fellowship. RS is supported by the Raelene Boyle Sporting Chance Foundation and Royal Australasian College of Surgeons (RACS) Foundation Scholarship, and the RACS Surgeon Scientist Program. This work was supported by funds from the Operational Infrastructure Support Program provided by the Victorian Government, Australia.