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CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth

Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor infiltrating myeloid cells (TIMs) are known to promote metastasis but the mechanisms underlying their collaboration with tumor cells remain unknown. Here we report an oncogenic role for microRNA in driving M...

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Autores principales: Mathsyaraja, Haritha, Thies, Katie, Taffany, David A., Deighan, Clayton, Liu, Tom, Yu, Lianbo, Fernandez, Soledad A., Shapiro, Charles, Otero, Jose, Timmers, Cynthia, Lustberg, Maryam B., Chalmers, Jeffrey, Leone, Gustavo, Ostrowski, Michael C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369473/
https://www.ncbi.nlm.nih.gov/pubmed/25241894
http://dx.doi.org/10.1038/onc.2014.294
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author Mathsyaraja, Haritha
Thies, Katie
Taffany, David A.
Deighan, Clayton
Liu, Tom
Yu, Lianbo
Fernandez, Soledad A.
Shapiro, Charles
Otero, Jose
Timmers, Cynthia
Lustberg, Maryam B.
Chalmers, Jeffrey
Leone, Gustavo
Ostrowski, Michael C.
author_facet Mathsyaraja, Haritha
Thies, Katie
Taffany, David A.
Deighan, Clayton
Liu, Tom
Yu, Lianbo
Fernandez, Soledad A.
Shapiro, Charles
Otero, Jose
Timmers, Cynthia
Lustberg, Maryam B.
Chalmers, Jeffrey
Leone, Gustavo
Ostrowski, Michael C.
author_sort Mathsyaraja, Haritha
collection PubMed
description Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor infiltrating myeloid cells (TIMs) are known to promote metastasis but the mechanisms underlying their collaboration with tumor cells remain unknown. Here we report an oncogenic role for microRNA in driving M2 reprogramming in TIMs, characterized by the acquisition of pro-tumor and pro-angiogenic properties. The expression of miR-21, miR-29a, miR-142-3p and miR-223 increased in myeloid cells during tumor progression in mouse models of breast cancer and melanoma metastasis. Further, we show that these miRs are regulated by the CSF1-ETS2 pathway in macrophages. A loss of function approach utilizing selective depletion of the microRNA processing enzyme Dicer in mature myeloid cells blocks angiogenesis and metastatic tumor growth. Ectopic expression of miR-21 and miR-29a promotes angiogenesis and tumor cell proliferation through the down-regulation of anti-angiogenic genes such as Col4a2, Spry1 and Timp3 whereas knockdown of the miRs impedes these processes. miR-21 and miR-29a are expressed in Csf1r+ myeloid cells associated with human metastatic breast cancer and levels of these miRs in CD115+ non-classical monocytes correlates with metastatic tumor burden in patients. Taken together, our results suggest that miR-21 and miR-29a are essential for the pro-tumor functions of myeloid cells and the CSF1-ETS2 pathway upstream of the miRs serves as an attractive therapeutic target for the inhibition of M2 remodeling of macrophages during malignancy. In addition, miR-21 and miR-29a in circulating myeloid cells may potentially serve as biomarkers to measure therapeutic efficacy of targeted therapies for CSF1 signaling.
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spelling pubmed-43694732016-01-01 CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth Mathsyaraja, Haritha Thies, Katie Taffany, David A. Deighan, Clayton Liu, Tom Yu, Lianbo Fernandez, Soledad A. Shapiro, Charles Otero, Jose Timmers, Cynthia Lustberg, Maryam B. Chalmers, Jeffrey Leone, Gustavo Ostrowski, Michael C. Oncogene Article Metastasis of solid tumors is associated with poor prognosis and bleak survival rates. Tumor infiltrating myeloid cells (TIMs) are known to promote metastasis but the mechanisms underlying their collaboration with tumor cells remain unknown. Here we report an oncogenic role for microRNA in driving M2 reprogramming in TIMs, characterized by the acquisition of pro-tumor and pro-angiogenic properties. The expression of miR-21, miR-29a, miR-142-3p and miR-223 increased in myeloid cells during tumor progression in mouse models of breast cancer and melanoma metastasis. Further, we show that these miRs are regulated by the CSF1-ETS2 pathway in macrophages. A loss of function approach utilizing selective depletion of the microRNA processing enzyme Dicer in mature myeloid cells blocks angiogenesis and metastatic tumor growth. Ectopic expression of miR-21 and miR-29a promotes angiogenesis and tumor cell proliferation through the down-regulation of anti-angiogenic genes such as Col4a2, Spry1 and Timp3 whereas knockdown of the miRs impedes these processes. miR-21 and miR-29a are expressed in Csf1r+ myeloid cells associated with human metastatic breast cancer and levels of these miRs in CD115+ non-classical monocytes correlates with metastatic tumor burden in patients. Taken together, our results suggest that miR-21 and miR-29a are essential for the pro-tumor functions of myeloid cells and the CSF1-ETS2 pathway upstream of the miRs serves as an attractive therapeutic target for the inhibition of M2 remodeling of macrophages during malignancy. In addition, miR-21 and miR-29a in circulating myeloid cells may potentially serve as biomarkers to measure therapeutic efficacy of targeted therapies for CSF1 signaling. 2014-09-22 2015-07 /pmc/articles/PMC4369473/ /pubmed/25241894 http://dx.doi.org/10.1038/onc.2014.294 Text en http://www.nature.com/authors/editorial_policies/license.html#terms Users may view, print, copy, and download text and data-mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use:http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Mathsyaraja, Haritha
Thies, Katie
Taffany, David A.
Deighan, Clayton
Liu, Tom
Yu, Lianbo
Fernandez, Soledad A.
Shapiro, Charles
Otero, Jose
Timmers, Cynthia
Lustberg, Maryam B.
Chalmers, Jeffrey
Leone, Gustavo
Ostrowski, Michael C.
CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title_full CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title_fullStr CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title_full_unstemmed CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title_short CSF1-ETS2 Induced microRNA in Myeloid Cells Promote Metastatic Tumor Growth
title_sort csf1-ets2 induced microrna in myeloid cells promote metastatic tumor growth
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4369473/
https://www.ncbi.nlm.nih.gov/pubmed/25241894
http://dx.doi.org/10.1038/onc.2014.294
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