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Endothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy

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Tumor Biology

Abstract

Endothelial progenitor cells (EPCs) have recently been shown to promote the angiogenic switch in solid neoplasms, thereby promoting tumour growth and metastatisation. The genetic suppression of EPC mobilization from bone marrow prevents tumour development and colonization of remote organs. Therefore, it has been assumed that anti-angiogenic treatments, which target vascular endothelial growth factor (VEGF) signalling in both normal endothelial cells and EPCs, could interfere with EPC activation in cancer patients. Our recent data, however, show that VEGF fails to stimulate tumour endothelial colony-forming cells (ECFCs), i.e. the only EPC subtype truly belonging to the endothelial lineage. The present article will survey current evidence about EPC involvement in the angiogenic switch: we will focus on the controversy about EPC definition and on the debate around their actual incorporation into tumour neovessels. We will then discuss how ECFC insensitivity to VEGF stimulation in cancer patients could underpin their well-known resistance to anti-VEGF therapies.

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Acknowledgments

This work was supported by a grant from the Cariplo Foundation [2010-0807] and by a grant from the Associazione Italiana per la Ricerca sul Cancro (AIRC; Milan, Italy), Special Program Molecular Clinical Oncology 5x1000 to AIRC-Gruppo Italiano Malattie Mieloproliferative (AGIMM) project #1005, both awarded to VR.

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Authors and Affiliations

  1. Laboratory of General Physiology, Department of Biology and Biotechnology “L. Spallanzani”, University of Pavia, via Forlanini 6, 27100, Pavia, Italy

    Francesco Moccia & Estella Zuccolo

  2. Unit of Clinical Epidemiology, Fondazione IRCCS Policlinico San Matteo, 27100, Pavia, Italy

    Valentina Poletto, Elisa Bonetti & Vittorio Rosti

  3. Department of Public Health, University of Naples “Federico II”, via Pansini 5, 80131, Naples, Italy

    Mariapia Cinelli

  4. Department of Medicine and Health Sciences “V. Tiberio”, University of Molise, Via F. De Santis, 86100, Campobasso, Italy

    Germano Guerra

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  1. Francesco Moccia
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  2. Estella Zuccolo
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  3. Valentina Poletto
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  4. Mariapia Cinelli
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  5. Elisa Bonetti
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  6. Germano Guerra
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  7. Vittorio Rosti
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Corresponding author

Correspondence to Francesco Moccia.

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Mariapia Cinelli passed away during the preparation of this manuscript.

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Moccia, F., Zuccolo, E., Poletto, V. et al. Endothelial progenitor cells support tumour growth and metastatisation: implications for the resistance to anti-angiogenic therapy. Tumor Biol. 36, 6603–6614 (2015). https://doi.org/10.1007/s13277-015-3823-2

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  • DOI: https://doi.org/10.1007/s13277-015-3823-2

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