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Metastasis

Planting metastasis early

Nature Reviews Cancer volume 17, page 75 (2017)Cite this article

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early disseminated cancer cells (DCCs) from HER2+ breast cancer are more likely to seed metastasis than those from established tumours

In the BALB-NeuT and MMTV-Her2 mouse models of breast cancer, Hosseini et al. and Harper, Sosa et al. showed that primary tumour cell dissemination occurs early after the induction of Her2, as hyperplasia becomes apparent. Hosseini et al. showed that as these tumours develop, there is a reduction in the ratio of DCCs to tumour size; this was also the case in 2,239 patients with breast cancer. They generated an early lesion gene signature, which was not induced in HER2− mouse mammary cancer cell lines but could be induced in these lines on treatment with progesterone. This suggests that both progesterone and HER2 pathway activation are important for the expression of the early lesion signature. Next, they showed that progesterone induced migration and stem-like features of early lesion-derived mammary cells but suppressed the migration of primary tumour cells. These effects of progesterone on early lesion cells were attenuated when progesterone-induced paracrine signals (PIPS; including WNT4) were inhibited.

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References

  1. Hosseini, H. et al. Early dissemination seeds metastasis in breast cancer. Nature 540, 552–558 (2016)

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  2. Harper, K. L. et al. Mechanism of early dissemination and metastasis in Her2+ mammary cancer. Nature 540, 588–592 (2016)

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Authors
  1. Gemma K. Alderton
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Alderton, G. Planting metastasis early. Nat Rev Cancer 17, 75 (2017). https://doi.org/10.1038/nrc.2017.4

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