Poster Presentation 27th Lorne Cancer Conference 2015

Using a Novel Peptide to Target Tumour Angiogenesis  (#239)

Prue Plummer 1 , Christin Gasch 1 , Vito Ferro 2 , Vivek Mittal 3 , Albert Mellick 1
  1. School of Medicine, Deakin University , Geelong Waurn Ponds Campus, VIC, Australia
  2. School of Chemistry and Molecular Biosciences, University of Queensland, St Lucia , QLD, Australia
  3. Neuberger Berman Lung Cancer Centre, Weill Cornell University Medical College, New York, United States

For a tumour to grow and spread it needs to undergo tumour angiogenesis. In this process host vasculature is enrolled to the tumour, resulting in new vessel development. Anti-angiogenic therapies are currently used for cancer treatment, however these serious side-effects as they also target normal vasculature. Bone marrow (BM)-derived endothelial progenitor cells (EPCs) play an important role in tumour angiogenesis and are mobilized in response to growth factors. We have previously shown that EPCs migrate from the BM to the tumour-stroma1,2 . Here we report the identification of a novel small RNA pathway required for regulation of EPC function and tumour angiogenesis. In this pathway microRNA (miR)-10b is up-regulated in EPCs, and tumour vasculature in response to tumour challenge. The expression of miR-10b was also found to be in the vasculature of aggressive late stage invasive ductal carcinoma using a novel fluorescent in situ hybridization method developed by our lab. We have also demonstrated that miR-10b can be targeted in vivo using an anti-miR encapsulated in stealth liposomes tagged with an RGD-peptide (to target tumour vasculature). This resulted in a significant decrease in tumour growth and EPC mobilization1. We are currently altering this system so that the liposome will be tagged with a novel EPC-peptide, thus resulting in directed delivery of the anti-miR to EPCs.  This method is believed to target tumour vasculature formed during angiogenesis, as opposed to vasculature already within the body. It is proposed that this approach may lead to new anti-angiogenic therapies which will significantly decrease the adverse side-effects associated with current anti-angiogenic treatments.

  1. Plummer PN, Freeman R, Taft R et al. MicroRNAs Regulate Tumor Angiogenesis Modulated by Endothelial Progenitor Cells. Cancer Research (2013) 73:341-52.
  2. Mellick AS, Plummer PN, Nolan D, et al. Using Transcription Factor Id1 to Selectively Target Endothelial Progenitor Cells Offers Novel Strategies to Inhibit Tumour Angiogenesis and Growth. Cancer Research (2010) 70:7273-82.