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A niche role for cancer exosomes in metastasis

Nature Cell Biology volume 17, pages 709–711 (2015)Cite this article

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Cancer cells are known to secrete exosomes with pro-metastatic effects. Pancreatic-cancer-derived exosomes are now shown to promote liver metastasis by eliciting pre-metastatic niche formation through a multi-step process. This involves uptake of exosome-derived factors by liver Kupffer cells and hepatic stellate cell activation to generate a fibrotic microenvironment with immune cell infiltrates that favours metastasis.

To form metastases at a distal organ, cancer cells have to successfully complete a series of distinct steps, which include invasion through the basement membrane, intravasation into the bloodstream, dissemination through the circulation, extravasation to the distal tissue parenchyma and adaptation to the foreign microenvironment1,2. Although the majority of disseminated cells fail to survive and proliferate after reaching a foreign tissue3, metastatic disease causes the death of approximately 90% of cancer patients4. Therefore, understanding the mechanisms through which certain cancer cells are able to grow at metastatic sites is a topic of high clinical importance. In several types of cancer, accumulating evidence supports the existence of metastasis-supportive microenvironments termed pre-metastatic niches, which form at the sites of future metastases to allow the colonization and growth of disseminated tumour cells5,6. For example, in malignant melanoma, primary tumour cells orchestrate pre-metastatic niche formation by directing bone marrow-derived cells (BMDCs) towards a pro-metastatic phenotype and promoting their mobilization to future metastatic sites including the lymph nodes and the lung7. This process is mediated by the systemic action of exosomes secreted from the primary melanoma cells7. Exosomes are small membrane-bound vesicles that are actively shed by a diverse population of normal and malignant cells8,9. Exosomes transfer RNAs and proteins to the cells they fuse with and play important roles in cell-to-cell communication10. Accumulating evidence suggests that exosomes also play an important role in cancer progression7,11. However, whether the dependence of pre-metastatic niche formation on tumour-derived exosomes is a general mechanism that functions in multiple cancer types has remained unclear. In this issue of Nature Cell Biology Costa-Silva et al. report12 that a cancer-exosome-mediated pathway promotes liver metastasis of pancreatic ductal adenocarcinoma (PDAC) cells, and describe the sequential steps of PDAC-exosome-induced pre-metastatic niche formation in the liver.

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Figure 1: The sequential steps in liver pre-metastatic niche formation induced by PDAC-derived exosomes.

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Authors and Affiliations

  1. Yun Zhang is at the Whitehead Institute for Biomedical Research, Cambridge, Massachusetts 02142, USA,

    Yun Zhang

  2. Xiao-Fan Wang is in the Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, North Carolina 27710, USA,

    Xiao-Fan Wang

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  1. Yun Zhang
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Correspondence to Xiao-Fan Wang.

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Zhang, Y., Wang, XF. A niche role for cancer exosomes in metastasis. Nat Cell Biol 17, 709–711 (2015). https://doi.org/10.1038/ncb3181

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