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Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells

Cancer cells are known to contain high levels of the heat shock protein 70 kDa (Hsp70), which mediates increased cell proliferation, escape from programmed cell death, enhanced invasion, and metastasis. A part of Hsp70 molecules may release from cancer cells and affect the behavior of adjacent strom...

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Autores principales: Komarova, Elena Y., Marchenko, Larisa V., Zhakhov, Alexander V., Nikotina, Alina D., Aksenov, Nikolay D., Suezov, Roman V., Ischenko, Alexander M., Margulis, Boris A., Guzhova, Irina V.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982218/
https://www.ncbi.nlm.nih.gov/pubmed/31861801
http://dx.doi.org/10.3390/ijms21010059
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author Komarova, Elena Y.
Marchenko, Larisa V.
Zhakhov, Alexander V.
Nikotina, Alina D.
Aksenov, Nikolay D.
Suezov, Roman V.
Ischenko, Alexander M.
Margulis, Boris A.
Guzhova, Irina V.
author_facet Komarova, Elena Y.
Marchenko, Larisa V.
Zhakhov, Alexander V.
Nikotina, Alina D.
Aksenov, Nikolay D.
Suezov, Roman V.
Ischenko, Alexander M.
Margulis, Boris A.
Guzhova, Irina V.
author_sort Komarova, Elena Y.
collection PubMed
description Cancer cells are known to contain high levels of the heat shock protein 70 kDa (Hsp70), which mediates increased cell proliferation, escape from programmed cell death, enhanced invasion, and metastasis. A part of Hsp70 molecules may release from cancer cells and affect the behavior of adjacent stromal cells. To explore the effects of Hsp70 on the status of monocytes/macrophages in the tumor locale, we incubated human carcinoma cells of three distinct lines with normal and reduced content of Hsp70 with THP1 monocytes. Using two methods, we showed that the cells with knock-down of Hsp70 released a lower amount of protein in the extracellular medium. Three cycles of the co-cultivation of cancer and monocytic cells led to the secretion of several cytokines typical of the tumor microenvironment (TME) and to pro-cancer activation of the monocytes/macrophages as established by elevation of F4/80 and arginase-1 markers. Unexpectedly, the efficacy of epithelial–mesenchymal transition and resistance of carcinoma cells to anticancer drugs after incubation with monocytic cells were more pronounced in cells with lower Hsp70, e.g., releasing less Hsp70 into the extracellular milieu. These data suggest that Hsp70 released from tumor cells into the TME is able, together with the development of an anti-cancer immune response, to limit the conversion of a considerable part of monocytic cells to the pro-tumor phenotype.
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spelling pubmed-69822182020-02-07 Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells Komarova, Elena Y. Marchenko, Larisa V. Zhakhov, Alexander V. Nikotina, Alina D. Aksenov, Nikolay D. Suezov, Roman V. Ischenko, Alexander M. Margulis, Boris A. Guzhova, Irina V. Int J Mol Sci Article Cancer cells are known to contain high levels of the heat shock protein 70 kDa (Hsp70), which mediates increased cell proliferation, escape from programmed cell death, enhanced invasion, and metastasis. A part of Hsp70 molecules may release from cancer cells and affect the behavior of adjacent stromal cells. To explore the effects of Hsp70 on the status of monocytes/macrophages in the tumor locale, we incubated human carcinoma cells of three distinct lines with normal and reduced content of Hsp70 with THP1 monocytes. Using two methods, we showed that the cells with knock-down of Hsp70 released a lower amount of protein in the extracellular medium. Three cycles of the co-cultivation of cancer and monocytic cells led to the secretion of several cytokines typical of the tumor microenvironment (TME) and to pro-cancer activation of the monocytes/macrophages as established by elevation of F4/80 and arginase-1 markers. Unexpectedly, the efficacy of epithelial–mesenchymal transition and resistance of carcinoma cells to anticancer drugs after incubation with monocytic cells were more pronounced in cells with lower Hsp70, e.g., releasing less Hsp70 into the extracellular milieu. These data suggest that Hsp70 released from tumor cells into the TME is able, together with the development of an anti-cancer immune response, to limit the conversion of a considerable part of monocytic cells to the pro-tumor phenotype. MDPI 2019-12-20 /pmc/articles/PMC6982218/ /pubmed/31861801 http://dx.doi.org/10.3390/ijms21010059 Text en © 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Komarova, Elena Y.
Marchenko, Larisa V.
Zhakhov, Alexander V.
Nikotina, Alina D.
Aksenov, Nikolay D.
Suezov, Roman V.
Ischenko, Alexander M.
Margulis, Boris A.
Guzhova, Irina V.
Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title_full Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title_fullStr Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title_full_unstemmed Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title_short Extracellular Hsp70 Reduces the Pro-Tumor Capacity of Monocytes/Macrophages Co-Cultivated with Cancer Cells
title_sort extracellular hsp70 reduces the pro-tumor capacity of monocytes/macrophages co-cultivated with cancer cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6982218/
https://www.ncbi.nlm.nih.gov/pubmed/31861801
http://dx.doi.org/10.3390/ijms21010059
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