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. 2015 Oct 21;107(1):5–11. doi: 10.1111/cas.12817

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© 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.

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Steps in the development of distant metastasis based on cancer stem cell theory. Distant metastasis of tumor cells occurs by way of several distinct steps: dissociation of cancer cells from the primary tumor after they have undergone epithelial–mesenchymal transition (1) is followed by their intravasation (2), circulation in the blood as CTCs (3), extravasation (4), and homing to the premetastatic niche and colonization of the metastatic site (5). Organ‐selective tumor metastasis may depend on whether the premetastatic niche is a favorable microenvironment for circulating cancer stem cells.