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Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23
Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone fo...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group UK
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560700/ https://www.ncbi.nlm.nih.gov/pubmed/33057033 http://dx.doi.org/10.1038/s41598-020-74352-x |
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author | Mulcrone, Patrick L. Edwards, Shanique K. E. Petrusca, Daniela N. Haneline, Laura S. Delgado-Calle, Jesús Roodman, G. David |
author_facet | Mulcrone, Patrick L. Edwards, Shanique K. E. Petrusca, Daniela N. Haneline, Laura S. Delgado-Calle, Jesús Roodman, G. David |
author_sort | Mulcrone, Patrick L. |
collection | PubMed |
description | Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increased Vegf-a expression in MLOA5-Ocys, and conditioned media (CM) from MLOA5s or MM-MLOA5 co-cultured in hypoxia, significantly increased endothelial tube length compared to normoxic CM. Further, Vegf-a knockdown in MLOA5s or primary Ocys co-cultured with MM cells or neutralizing Vegf-a in MM-Ocy co-culture CM completely blocked the increased endothelial activity. Importantly, Vegf-a-expressing Ocy numbers were significantly increased in MM-injected mouse bones, positively correlating with tumor vessel area. Finally, we demonstrate that direct contact with MM cells increases Ocy Fgf23, which enhanced Vegf-a expression in Ocys. Fgf23 deletion in Ocys blocked these changes. These results suggest hypoxia and MM cells induce a pro-angiogenic phenotype in Ocys via Fgf23 and Vegf-a signaling, which can promote MM-induced marrow vascularization. |
format | Online Article Text |
id | pubmed-7560700 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Nature Publishing Group UK |
record_format | MEDLINE/PubMed |
spelling | pubmed-75607002020-10-19 Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 Mulcrone, Patrick L. Edwards, Shanique K. E. Petrusca, Daniela N. Haneline, Laura S. Delgado-Calle, Jesús Roodman, G. David Sci Rep Article Multiple Myeloma (MM) induces bone destruction, decreases bone formation, and increases marrow angiogenesis in patients. We reported that osteocytes (Ocys) directly interact with MM cells to increase tumor growth and expression of Ocy-derived factors that promote bone resorption and suppress bone formation. However, the contribution of Ocys to enhanced marrow vascularization in MM is unclear. Since the MM microenvironment is hypoxic, we assessed if hypoxia and/or interactions with MM cells increases pro-angiogenic signaling in Ocys. Hypoxia and/or co-culture with MM cells significantly increased Vegf-a expression in MLOA5-Ocys, and conditioned media (CM) from MLOA5s or MM-MLOA5 co-cultured in hypoxia, significantly increased endothelial tube length compared to normoxic CM. Further, Vegf-a knockdown in MLOA5s or primary Ocys co-cultured with MM cells or neutralizing Vegf-a in MM-Ocy co-culture CM completely blocked the increased endothelial activity. Importantly, Vegf-a-expressing Ocy numbers were significantly increased in MM-injected mouse bones, positively correlating with tumor vessel area. Finally, we demonstrate that direct contact with MM cells increases Ocy Fgf23, which enhanced Vegf-a expression in Ocys. Fgf23 deletion in Ocys blocked these changes. These results suggest hypoxia and MM cells induce a pro-angiogenic phenotype in Ocys via Fgf23 and Vegf-a signaling, which can promote MM-induced marrow vascularization. Nature Publishing Group UK 2020-10-14 /pmc/articles/PMC7560700/ /pubmed/33057033 http://dx.doi.org/10.1038/s41598-020-74352-x Text en © The Author(s) 2020 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Article Mulcrone, Patrick L. Edwards, Shanique K. E. Petrusca, Daniela N. Haneline, Laura S. Delgado-Calle, Jesús Roodman, G. David Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title | Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title_full | Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title_fullStr | Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title_full_unstemmed | Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title_short | Osteocyte Vegf-a contributes to myeloma-associated angiogenesis and is regulated by Fgf23 |
title_sort | osteocyte vegf-a contributes to myeloma-associated angiogenesis and is regulated by fgf23 |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7560700/ https://www.ncbi.nlm.nih.gov/pubmed/33057033 http://dx.doi.org/10.1038/s41598-020-74352-x |
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