Volume 12 Supplement 1

Melanoma Bridge 2013: Poster and Oral Presentations

Open Access

A novel approach to target metastases of melanoma cells in an organ-selective manner

  • Saurav Roy Choudhury1,
  • Jennifer Rahn1, 2,
  • Xiaoguang Hao1,
  • Liane Babes3,
  • Paul Kubes3,
  • Stephen M Robbins1, 2 and
  • Donna L Senger1Email author
Contributed equally
Journal of Translational Medicine201412(Suppl 1):P2

https://doi.org/10.1186/1479-5876-12-S1-P2

Published: 6 May 2014

Background

Cancer is a leading cause of death globally and the majority of patients will die from the formation of metastases rather than from their primary tumour as most metastases are resistant to conventional therapies. Based on numerous clinical observations it is clear that different cancers have a propensity to metastasize to specific organs. The central hypothesis for our current study is that an organs vasculature is intimately involved in mediating the interaction between specific cancer cells and the target organ for which they will metastasize to. In this respect we have focused on how melanoma cancer cells metastasize to the liver and lungs, two major sites of metastatic disease within the body, in order to provide insight for the development of new treatments for metastatic cancer.

Materials and methods

Herein we used an unbiased combinatorial phage in vivo biopanning strategy to isolate a library of peptide-displaying-phage that home to the liver and lungs of animals treated with a pro-inflammatory stimulus, lipopolysccharaide (LPS). Using a functional screen we isolated a single phage that prevented the recruitment of leukocytes into the liver and lungs of animals following LPS treatment. We investigated if the lung/liver inhibitory phage were also able to inhibit the formation of lung metastasis using a human melanoma metastasis xenograft model.

Results

Using intravital microscopy, we identified a peptide-displaying-phage, and its corresponding displayed-peptide, that has the ability to inhibit adhesion and recruitment of neutrophils in the liver sinusoids in response to LPS. Excitingly, we also found that animals injected (i.v.) with human melanoma cells (70W) in the presence of the phage, or its corresponding displayed-peptide, showed reduced metastatic lung burden. As the isolated peptide was capable of inhibiting both leukocyte recruitment and melanoma lung metastasis, we asked if leukocytes played a functional role in the establishment of melanoma metastasis. We found that in animals that received Lys6G (Anti Gr-1) antibody to deplete circulating leukocytes there was a dramatic increase in 70W melanoma metastasis to the lungs and that this increase in metastatic state was still blocked by the addition of the peptide.

Conclusion

These results suggest two major findings, first that circulating leukocytes could have a protective role in preventing melanoma metastasis to the lungs and second that the peptide identified in this study may work by blocking molecules that are required for recruitment and/or extravasation of the cancer cells, a process that is shared by leukocytes.

Notes

Authors’ Affiliations

(1)
Department of Oncology, University of Calgary and Southern Alberta Cancer Research Institute
(2)
Department of Biochemistry and Molecular Biology, University of Calgary
(3)
Snyder Institute for Chronic Diseases, Department of Physiology and Pharmacology, University of Calgary

Copyright

© Choudhury et al; licensee BioMed Central Ltd. 2014

This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

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