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Functional genomics of endothelial cells treated with anti-angiogenic or angiopreventive drugs

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Abstract

Angiogenesis is a highly regulated physiological process that has been studied in considerable detail given its importance in several chronic pathologies. Many endogenous factors and hormones intervene in the regulation of angiogensis and classical as well as targeted drugs have been developed for its control. Angiogenesis inhibition has come off the bench and entered into clinical application for cancer therapy, particularly for metastatic disease. While the clinical benefit is currently in terms of months, preclinical data suggest that novel drugs and drug combinations could lead to substantial improvement. The many targets of endogenous angiogenesis inhibitors reflect the complexity of the process; in contrast, current clinical therapies mainly target the vascular endothelial growth factor system. Cancer chemopreventive compounds can retard tumor insurgence and delay or prevent metastasis and many of these molecules hinder angiogenesis, a mechanism that we termed angioprevention. Angiopreventive drugs appear to prevalently act through the inhibition of the pro-inflammatory and anti-apoptotic player NFκB, thus contrasting inflammation dependent angiogenesis. Relatively little is known concerning the effects of these angiogenesis inhibitors on gene expression of endothelial cells, the main target of many of these molecules. Here we provide an exhaustive list of anti-angiogenic molecules, and summarize their effects, where known, on the transcriptome and functional genomics of endothelial cells. The regulation of specific genes can be crucial to preventive or therapeutic intervention. Further, novel targets might help to circumvent resistance to anti-angiogenic therapy. The studies we review are relevant not only to cancer but also to other chronic degenerative diseases involving endothelial cells, such as cardiovascular disorders, diabetes, rheumatoid arthritis and retinopaties, as well as vessel aging.

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Acknowledgments

This work has been made possible by contributions from the Italian Health Ministry to UP, the Regione Liguria to UP, the Compagnia San Paolo di Torino to UP and AA, the AIRC (Associazione Italiana per la Ricerca sul Cancro; to DN and AA), the Ministero della Salute (to AA and DN), and the Università degli Studi dell’Insubria (to DN). AA is the recipient of a Berlucchi Award for Scientific Research.

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Authors and Affiliations

  1. MultiMedica Castellanza (VA) and Oncology Research, IRCCS MultiMedica, Via Fantoli 16/15, 20138, Milan, Italy

    Adriana Albini

  2. Dr. Stefano Indraccolo Istituto Oncologico Veneto – IRCCS, via Gattamelata 64, 35128, Padova, Italy

    Stefano Indraccolo

  3. Department of Experimental Medicine, University of Insubria, Viale Ottorino Rossi 9, 21100, Varese, Italy

    Douglas M. Noonan

  4. Functional Genomics, National Cancer Research Institute, Largo Rosanna Benzi 10, 16132, Genova, Italy

    Ulrich Pfeffer

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  1. Adriana Albini
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  2. Stefano Indraccolo
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Correspondence to Douglas M. Noonan.

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Albini, A., Indraccolo, S., Noonan, D.M. et al. Functional genomics of endothelial cells treated with anti-angiogenic or angiopreventive drugs. Clin Exp Metastasis 27, 419–439 (2010). https://doi.org/10.1007/s10585-010-9312-5

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