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. 2015 Jun 26;4(12):e1048955. doi: 10.1080/2162402X.2015.1048955

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© 2015 The Author(s). Published with license by Taylor & Francis Group, LLC

© Shawn C Chafe and Shoukat Dedhar

This is an Open Access article distributed under the terms of the Creative Commons Attribution-Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. The moral rights of the named author(s) have been asserted.

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Figure 1. — A model for CAIX-driven pre-metastatic niche development. Secreted factors originating from the hypoxic cancer cells within the primary tumor stimulate bone marrow-derived cell (BMDC) egress from the bone marrow. Granulocyte colony stimulating factor (G-CSF) is a key factor involved in the mobilization of immunosuppressive granulocytic myeloid-derived suppressor cells (MDSCs) to the pre-metastatic lung, thereby initiating an environment conducive to the establishment of metastatic growth. Hypoxic cancer cells (inset, right) found within poorly oxygenated regions of the tumor upregulate carbonic anhydrase IX (CAIX) expression, stimulating nuclear factor κB (NF-κB) activity and the subsequent production of G-CSF.