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BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells
The hypoxia responsive protein BNIP3, plays an important role in promoting cell death and/or autophagy, ultimately resulting in a cancer type-dependent, tumour-enhancer or tumour-suppressor activity. We previously reported that in melanoma cells, BNIP3 regulates cellular morphology, mitochondrial cl...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915144/ https://www.ncbi.nlm.nih.gov/pubmed/29707136 http://dx.doi.org/10.18632/oncotarget.24815 |
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author | Romano, Erminia Rufo, Nicole Korf, Hannelie Mathieu, Chantal Garg, Abhishek D. Agostinis, Patrizia |
author_facet | Romano, Erminia Rufo, Nicole Korf, Hannelie Mathieu, Chantal Garg, Abhishek D. Agostinis, Patrizia |
author_sort | Romano, Erminia |
collection | PubMed |
description | The hypoxia responsive protein BNIP3, plays an important role in promoting cell death and/or autophagy, ultimately resulting in a cancer type-dependent, tumour-enhancer or tumour-suppressor activity. We previously reported that in melanoma cells, BNIP3 regulates cellular morphology, mitochondrial clearance, cellular viability and maintains protein expression of CD47, a pro-cancerous, immunosuppressive 'don't eat me' signal. Surface exposed CD47 is often up-regulated by cancer cells to avoid clearance by phagocytes and to suppress immunogenic cell death (ICD) elicited by anticancer therapies. However, whether melanoma-associated BNIP3 modulates CD47-associated immunological effects or ICD has not been explored properly. To this end, we evaluated the impact of the genetic ablation of BNIP3 (i.e. BNIP3(KD)) in melanoma cells, on macrophage-based phagocytosis, polarization and chemotaxis. Additionally, we tested its effects on crucial determinants of chemotherapy-induced ICD (i.e. danger signals), as well as in vivo anticancer vaccination effect. Interestingly, loss of BNIP3 reduced the expression of CD47 both in normoxic and hypoxic conditions while macrophage phagocytosis and chemotaxis were accentuated only when BNIP3(KD) melanoma cells were exposed to hypoxia. Moreover, when exposed to the ICD inducer mitoxantrone, the loss of melanoma cell-associated BNIP3 did not alter apoptosis induction, but significantly prevented ATP secretion and reduced phagocytic clearance of dying cells. In line with this, prophylactic vaccination experiments showed that the loss of BNIP3 tends to increase the intrinsic resistance of B16-F10 melanoma cells to ICD-associated anticancer vaccination effect in vivo. Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. |
format | Online Article Text |
id | pubmed-5915144 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59151442018-04-27 BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells Romano, Erminia Rufo, Nicole Korf, Hannelie Mathieu, Chantal Garg, Abhishek D. Agostinis, Patrizia Oncotarget Research Paper The hypoxia responsive protein BNIP3, plays an important role in promoting cell death and/or autophagy, ultimately resulting in a cancer type-dependent, tumour-enhancer or tumour-suppressor activity. We previously reported that in melanoma cells, BNIP3 regulates cellular morphology, mitochondrial clearance, cellular viability and maintains protein expression of CD47, a pro-cancerous, immunosuppressive 'don't eat me' signal. Surface exposed CD47 is often up-regulated by cancer cells to avoid clearance by phagocytes and to suppress immunogenic cell death (ICD) elicited by anticancer therapies. However, whether melanoma-associated BNIP3 modulates CD47-associated immunological effects or ICD has not been explored properly. To this end, we evaluated the impact of the genetic ablation of BNIP3 (i.e. BNIP3(KD)) in melanoma cells, on macrophage-based phagocytosis, polarization and chemotaxis. Additionally, we tested its effects on crucial determinants of chemotherapy-induced ICD (i.e. danger signals), as well as in vivo anticancer vaccination effect. Interestingly, loss of BNIP3 reduced the expression of CD47 both in normoxic and hypoxic conditions while macrophage phagocytosis and chemotaxis were accentuated only when BNIP3(KD) melanoma cells were exposed to hypoxia. Moreover, when exposed to the ICD inducer mitoxantrone, the loss of melanoma cell-associated BNIP3 did not alter apoptosis induction, but significantly prevented ATP secretion and reduced phagocytic clearance of dying cells. In line with this, prophylactic vaccination experiments showed that the loss of BNIP3 tends to increase the intrinsic resistance of B16-F10 melanoma cells to ICD-associated anticancer vaccination effect in vivo. Thus, normoxic vs. hypoxic and live vs. dying cell contexts influence the ultimate immunomodulatory roles of melanoma cell-associated BNIP3. Impact Journals LLC 2018-04-03 /pmc/articles/PMC5915144/ /pubmed/29707136 http://dx.doi.org/10.18632/oncotarget.24815 Text en Copyright: © 2018 Romano 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/) 3.0 (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Romano, Erminia Rufo, Nicole Korf, Hannelie Mathieu, Chantal Garg, Abhishek D. Agostinis, Patrizia BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title | BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title_full | BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title_fullStr | BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title_full_unstemmed | BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title_short | BNIP3 modulates the interface between B16-F10 melanoma cells and immune cells |
title_sort | bnip3 modulates the interface between b16-f10 melanoma cells and immune cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915144/ https://www.ncbi.nlm.nih.gov/pubmed/29707136 http://dx.doi.org/10.18632/oncotarget.24815 |
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