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Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis

Oncogene volume 32, pages 1530–1538 (2013)Cite this article

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A Corrigendum to this article was published on 14 November 2016

Abstract

Metastases, and not the primary tumor from which they originate, are the main reason for mortality from carcinoma. Although the molecular mechanisms behind metastasis are poorly understood, it is clear that epigenetic dysregulation at the level of microRNA expression is a key characteristic of the metastatic process that can be exploited for therapy. Here, we describe an miRNA-targeted therapeutic approach for the prevention and arrest of lymph node metastasis. Therapy relies on the inhibition of the pro-metastatic microRNA-10b. It is delivered to primary and lymph node metastatic tumor cells using an imaging-capable nanodrug that is designed to specifically home to these tissues. Treatment of invasive human breast tumor cells (MDA-MB-231) with the nanodrug in vitro downregulates miR-10b and abolishes the invasion and migration of the tumor cells. After intravenous delivery to mice bearing orthotopic MDA-MB-231-luc-D3H2LN tumors, the nanodrug accumulates in the primary tumor and lymph nodes. When treatment is initiated before metastasis to lymph nodes, metastasis is prevented. Treatment after the formation of lymph node metastases arrests the metastatic process without a concomitant effect on primary tumor growth raising the possibility of a context-dependent variation in miR-10b breast oncogenesis.

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Acknowledgements

We thank Pamela Pantazopoulos and Alana Ross for help with the in-vitro, in-vivo and ex-vivo studies and Marytheresa Ifediba for proofreading the manuscript. Confocal microscopy was performed at the Confocal Microscopy Core at MGH with technical assistance from Igor A Bagayev, MS Work at the Martinos Center for Biomedical Imaging was supported in part under Grant R00CA129070 from the National Cancer Institute and a Research Grant from the Breast Cancer Alliance.

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Authors and Affiliations

  1. Department of Radiology, Molecular Imaging Laboratory, Athinoula A Martinos Center for Biomedical Imaging, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA, USA

    M V Yigit, S K Ghosh, M Kumar, A Kavishwar, A Moore & Z Medarova

  2. Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA, USA

    V Petkova

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  1. M V Yigit
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  2. S K Ghosh
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  3. M Kumar
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  4. V Petkova
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  5. A Kavishwar
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  6. A Moore
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  7. Z Medarova
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Correspondence to A Moore or Z Medarova.

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The authors declare no conflict of interest.

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Supplementary Information accompanies the paper on the Oncogene website

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Yigit, M., Ghosh, S., Kumar, M. et al. Context-dependent differences in miR-10b breast oncogenesis can be targeted for the prevention and arrest of lymph node metastasis. Oncogene 32, 1530–1538 (2013). https://doi.org/10.1038/onc.2012.173

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