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. 2018 Jul 16;4:18. doi: 10.1038/s41523-018-0071-9

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© The Author(s) 2018

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 1 — Exosomes of disseminated CSCs (a) with bulk cells of a primary tumor (PT) cooperating in the formation of a local metastatic niche near the tumor mass. We speculate that during further migration of tumor cells, the effects of migrating CSC-derived exosomes may have more impact than of exosomes secreted by the distant tumor mass (b). Induction of CAF differentiation is probably a multistep process (i.e., NF-activated fibroblast-CAF sequence). It is accompanied by the appearance of the tumor promoting effects of CAFs (c). CSC-derived exosomes are detectable both in the lymphatics and in blood circulation. They may originate from the stroma and may either annihilate the endothelial tight junctions (d) or they undergo an active transport by the endothelial cells (e). Evidently, these exosomes may also originate from circulating CSCs and may play a role in the formation of pro-metastatic site in distant organs (f)