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Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer

We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whe...

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Autores principales: Yoshimura, Teizo, Nakamura, Kaoru, Li, Chunning, Fujisawa, Masayoshi, Shiina, Tsuyoshi, Imamura, Mayu, Li, Tiantian, Mukaida, Naofumi, Matsukawa, Akihiro
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941073/
https://www.ncbi.nlm.nih.gov/pubmed/31888216
http://dx.doi.org/10.3390/ijms20246342
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author Yoshimura, Teizo
Nakamura, Kaoru
Li, Chunning
Fujisawa, Masayoshi
Shiina, Tsuyoshi
Imamura, Mayu
Li, Tiantian
Mukaida, Naofumi
Matsukawa, Akihiro
author_facet Yoshimura, Teizo
Nakamura, Kaoru
Li, Chunning
Fujisawa, Masayoshi
Shiina, Tsuyoshi
Imamura, Mayu
Li, Tiantian
Mukaida, Naofumi
Matsukawa, Akihiro
author_sort Yoshimura, Teizo
collection PubMed
description We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whether 4T1 cell-derived GM-CSF contributes to the expression of these genes by 4T1tumors, and their subsequent progression. Intraperitoneal injection of anti-GM-CSF neutralizing antibody did not decrease the expression of Mcp-1, Ccl17 or Rankl mRNA by 4T1 tumors. To further examine the role of cancer cell-derived GM-CSF, we generated GM-CSF-deficient 4T1 cells by using the Crisper-Cas9 system. As previously demonstrated, 4T1 cells are a mixture of cells and cloning of cells by itself significantly reduced tumor growth and lung metastasis. By contrast, GM-CSF-deficiency did not affect tumor growth, lung metastasis or the expression of these chemokine and cytokine genes in tumor tissues. By in-situ hybridization, the expression of Mcp-1 mRNA was detected in both F4/80-expressing and non-expressing cells in tumors of GM-CSF-deficient cells. These results indicate that cancer cell-derived GM-CSF is dispensable for the tuning of the 4T1 tumor microenvironment and the production of MCP-1, CCL17 or RANKL in the 4T1 tumor microenvironment is likely regulated by redundant mechanisms.
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spelling pubmed-69410732020-01-09 Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer Yoshimura, Teizo Nakamura, Kaoru Li, Chunning Fujisawa, Masayoshi Shiina, Tsuyoshi Imamura, Mayu Li, Tiantian Mukaida, Naofumi Matsukawa, Akihiro Int J Mol Sci Article We previously reported that 4T1 murine breast cancer cells produce GM-CSF that up-regulates macrophage expression of several cancer promoting genes, including Mcp-1/Ccl2, Ccl17 and Rankl, suggesting a critical role of cancer cell-derived GM-CSF in cancer progression. Here, we attempted to define whether 4T1 cell-derived GM-CSF contributes to the expression of these genes by 4T1tumors, and their subsequent progression. Intraperitoneal injection of anti-GM-CSF neutralizing antibody did not decrease the expression of Mcp-1, Ccl17 or Rankl mRNA by 4T1 tumors. To further examine the role of cancer cell-derived GM-CSF, we generated GM-CSF-deficient 4T1 cells by using the Crisper-Cas9 system. As previously demonstrated, 4T1 cells are a mixture of cells and cloning of cells by itself significantly reduced tumor growth and lung metastasis. By contrast, GM-CSF-deficiency did not affect tumor growth, lung metastasis or the expression of these chemokine and cytokine genes in tumor tissues. By in-situ hybridization, the expression of Mcp-1 mRNA was detected in both F4/80-expressing and non-expressing cells in tumors of GM-CSF-deficient cells. These results indicate that cancer cell-derived GM-CSF is dispensable for the tuning of the 4T1 tumor microenvironment and the production of MCP-1, CCL17 or RANKL in the 4T1 tumor microenvironment is likely regulated by redundant mechanisms. MDPI 2019-12-16 /pmc/articles/PMC6941073/ /pubmed/31888216 http://dx.doi.org/10.3390/ijms20246342 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
Yoshimura, Teizo
Nakamura, Kaoru
Li, Chunning
Fujisawa, Masayoshi
Shiina, Tsuyoshi
Imamura, Mayu
Li, Tiantian
Mukaida, Naofumi
Matsukawa, Akihiro
Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title_full Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title_fullStr Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title_full_unstemmed Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title_short Cancer Cell-Derived Granulocyte-Macrophage Colony-Stimulating Factor Is Dispensable for the Progression of 4T1 Murine Breast Cancer
title_sort cancer cell-derived granulocyte-macrophage colony-stimulating factor is dispensable for the progression of 4t1 murine breast cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6941073/
https://www.ncbi.nlm.nih.gov/pubmed/31888216
http://dx.doi.org/10.3390/ijms20246342
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