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Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis
Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor–promoting microenvironment. However, subsets of myeloid cells have also been reported to have anti-tumor properties. It is not clear whether there is a transition between anti- and pro- tumor function of these myelo...
Autores principales: | , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2016
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438604/ https://www.ncbi.nlm.nih.gov/pubmed/27223426 http://dx.doi.org/10.18632/oncotarget.9486 |
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author | Jian, Jiang Pang, Yanli Yan, H. Hannah Min, Yongfen Achyut, Bhagelu R. Hollander, M. Christine Lin, P. Charles Liang, Xinhua Yang, Li |
author_facet | Jian, Jiang Pang, Yanli Yan, H. Hannah Min, Yongfen Achyut, Bhagelu R. Hollander, M. Christine Lin, P. Charles Liang, Xinhua Yang, Li |
author_sort | Jian, Jiang |
collection | PubMed |
description | Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor–promoting microenvironment. However, subsets of myeloid cells have also been reported to have anti-tumor properties. It is not clear whether there is a transition between anti- and pro- tumor function of these myeloid cells, and if so, what are the underlying molecular mechanisms. Here we report platelet factor 4 (PF4), or CXCL4, but not the other family members CXCL9, 10, and 11, was produced at higher levels in the normal lung and early stage premetastatic lungs but decreased in later stage lungs. PF4 was mostly produced by Ly6G+CD11b+ myeloid cell subset. Although the number of Ly6G+CD11b+ cells was increased in the premetastatic lungs, the expression level of PF4 in these cells was decreased during the metastatic progression. Deletion of PF4 (PF4 knockout or KO mice) led an increased metastasis suggesting an inhibitory function of PF4. There were two underlying mechanisms: decreased blood vessel integrity in the premetastatic lungs and increased production of hematopoietic stem/progenitor cells (HSCs) and myeloid derived suppressor cells (MDSCs) in tumor-bearing PF4 KO mice. In cancer patients, PF4 expression levels were negatively correlated with tumor stage and positively correlated with patient survival. Our studies suggest that PF4 is a critical anti-tumor factor in the premetastatic site. Our finding of PF4 function in the tumor host provides new insight to the mechanistic understanding of tumor metastasis. |
format | Online Article Text |
id | pubmed-5438604 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2016 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54386042017-05-24 Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis Jian, Jiang Pang, Yanli Yan, H. Hannah Min, Yongfen Achyut, Bhagelu R. Hollander, M. Christine Lin, P. Charles Liang, Xinhua Yang, Li Oncotarget Research Paper Bone marrow-derived myeloid cells can form a premetastatic niche and provide a tumor–promoting microenvironment. However, subsets of myeloid cells have also been reported to have anti-tumor properties. It is not clear whether there is a transition between anti- and pro- tumor function of these myeloid cells, and if so, what are the underlying molecular mechanisms. Here we report platelet factor 4 (PF4), or CXCL4, but not the other family members CXCL9, 10, and 11, was produced at higher levels in the normal lung and early stage premetastatic lungs but decreased in later stage lungs. PF4 was mostly produced by Ly6G+CD11b+ myeloid cell subset. Although the number of Ly6G+CD11b+ cells was increased in the premetastatic lungs, the expression level of PF4 in these cells was decreased during the metastatic progression. Deletion of PF4 (PF4 knockout or KO mice) led an increased metastasis suggesting an inhibitory function of PF4. There were two underlying mechanisms: decreased blood vessel integrity in the premetastatic lungs and increased production of hematopoietic stem/progenitor cells (HSCs) and myeloid derived suppressor cells (MDSCs) in tumor-bearing PF4 KO mice. In cancer patients, PF4 expression levels were negatively correlated with tumor stage and positively correlated with patient survival. Our studies suggest that PF4 is a critical anti-tumor factor in the premetastatic site. Our finding of PF4 function in the tumor host provides new insight to the mechanistic understanding of tumor metastasis. Impact Journals LLC 2016-05-19 /pmc/articles/PMC5438604/ /pubmed/27223426 http://dx.doi.org/10.18632/oncotarget.9486 Text en Copyright: © 2017 Jian et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Jian, Jiang Pang, Yanli Yan, H. Hannah Min, Yongfen Achyut, Bhagelu R. Hollander, M. Christine Lin, P. Charles Liang, Xinhua Yang, Li Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title | Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title_full | Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title_fullStr | Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title_full_unstemmed | Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title_short | Platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
title_sort | platelet factor 4 is produced by subsets of myeloid cells in premetastatic lung and inhibits tumor metastasis |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5438604/ https://www.ncbi.nlm.nih.gov/pubmed/27223426 http://dx.doi.org/10.18632/oncotarget.9486 |
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