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Immunology

Pro-metastatic TReg cells get RANKed

Nature Reviews Cancer volume 11, pages 234–235 (2011)Cite this article

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RANKL and its receptor, RANK (also known as TNFRSF11A), are involved in normal mammary cell proliferation and have been implicated in prostate cancer cell migration and bone metastasis, but the source of intratumoural RANKL and its role in metastasis are unknown. Thus, the authors used a mouse model of metastatic breast cancer to investigate the involvement of RANK signalling in mammary tumour metastasis. Rank+/− mice overexpressing the proto-oncogene Erbb2 in the mammary epithelium developed tumours with decreased RANK expression and displayed 50% fewer lung metastases than Rank+/+ controls. In addition, silencing or blocking of RANK in an orthotopic tumour model resulted in reduced pulmonary metastasis. By contrast, RANKL administration in mice with RANK+ human or mouse mammary tumours significantly increased the metastatic incidence.

The authors report that the engagement of RANK by its ligand induces the activation of IκB kinase-α (IKKα) and thereby represses expression of the metastasis inhibitor serpin B5 (also known as maspin). Moreover, RANKL treatment did not affect cancer cell motility or primary tumour growth, but increased the extravasation of circulating tumour cells in the lung and enhanced their survival.

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ORIGINAL RESEARCH PAPER

  1. Tan, W. et al. Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL–RANK signalling. Nature 470, 548–553 (2011)

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  1. Associate Editor, Nature Reviews Immunology,

    Maria Papatriantafyllou

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  1. Maria Papatriantafyllou
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Papatriantafyllou, M. Pro-metastatic TReg cells get RANKed. Nat Rev Cancer 11, 234–235 (2011). https://doi.org/10.1038/nrc3049

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