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Hypoxia activates placental growth factor expression in lymphatic endothelial cells
Placental growth factor (PlGF), a proangiogenic member of vascular endothelial growth family, is active during pathological conditions like cancer, metastasis formation and hind limb ischemia and in wound healing. Endothelial cells express PlGF and hypoxia positively modulates in vitro its expressio...
Autores principales: | , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464835/ https://www.ncbi.nlm.nih.gov/pubmed/28427198 http://dx.doi.org/10.18632/oncotarget.15861 |
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author | Tudisco, Laura Orlandi, Augusto Tarallo, Valeria De Falco, Sandro |
author_facet | Tudisco, Laura Orlandi, Augusto Tarallo, Valeria De Falco, Sandro |
author_sort | Tudisco, Laura |
collection | PubMed |
description | Placental growth factor (PlGF), a proangiogenic member of vascular endothelial growth family, is active during pathological conditions like cancer, metastasis formation and hind limb ischemia and in wound healing. Endothelial cells express PlGF and hypoxia positively modulates in vitro its expression. To verify whether hypoxia modulates PlGF expression in different cellular contexts and in vivo, we first analyzed five human and five mouse cancer cell lines showing that in eight of them hypoxia positively modulates PlGF. Next, we analyzed xenograft colorectal cancer tumors showing that human cancer cells were able to express PlGF in hypoxic area of the tumor. Surprisingly, we did not visualize mouse PlGF in CD31 positive tumor vessels, but in low CD31 positive vessels, a characteristic of lymphatic vessels. We found that hypoxia effectively activates PlGF expression in lymphatic endothelial cells as well as in LYVE1 positive tumor vessels. We also investigated two additional mouse angiogenic models, hind limb ischemia and wound healing, and we confirmed that lymphatic vessels of both ischemic muscles and skin express PlGF. These results show for the first time that hypoxia activates PlGF expression in lymphatic endothelial cells, which have to be considered an additional source for PlGF production in pathological contexts. |
format | Online Article Text |
id | pubmed-5464835 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-54648352017-06-21 Hypoxia activates placental growth factor expression in lymphatic endothelial cells Tudisco, Laura Orlandi, Augusto Tarallo, Valeria De Falco, Sandro Oncotarget Research Paper Placental growth factor (PlGF), a proangiogenic member of vascular endothelial growth family, is active during pathological conditions like cancer, metastasis formation and hind limb ischemia and in wound healing. Endothelial cells express PlGF and hypoxia positively modulates in vitro its expression. To verify whether hypoxia modulates PlGF expression in different cellular contexts and in vivo, we first analyzed five human and five mouse cancer cell lines showing that in eight of them hypoxia positively modulates PlGF. Next, we analyzed xenograft colorectal cancer tumors showing that human cancer cells were able to express PlGF in hypoxic area of the tumor. Surprisingly, we did not visualize mouse PlGF in CD31 positive tumor vessels, but in low CD31 positive vessels, a characteristic of lymphatic vessels. We found that hypoxia effectively activates PlGF expression in lymphatic endothelial cells as well as in LYVE1 positive tumor vessels. We also investigated two additional mouse angiogenic models, hind limb ischemia and wound healing, and we confirmed that lymphatic vessels of both ischemic muscles and skin express PlGF. These results show for the first time that hypoxia activates PlGF expression in lymphatic endothelial cells, which have to be considered an additional source for PlGF production in pathological contexts. Impact Journals LLC 2017-03-02 /pmc/articles/PMC5464835/ /pubmed/28427198 http://dx.doi.org/10.18632/oncotarget.15861 Text en Copyright: © 2017 Tudisco et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Tudisco, Laura Orlandi, Augusto Tarallo, Valeria De Falco, Sandro Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title | Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title_full | Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title_fullStr | Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title_full_unstemmed | Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title_short | Hypoxia activates placental growth factor expression in lymphatic endothelial cells |
title_sort | hypoxia activates placental growth factor expression in lymphatic endothelial cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5464835/ https://www.ncbi.nlm.nih.gov/pubmed/28427198 http://dx.doi.org/10.18632/oncotarget.15861 |
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