Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.

MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells...

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Autores principales: Teizo Yoshimura, O M Zack Howard, Toshihiro Ito, Masaki Kuwabara, Akihiro Matsukawa, Keqiang Chen, Ying Liu, Mingyong Liu, Joost J Oppenheim, Ji Ming Wang
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Publicado: Public Library of Science (PLoS) 2013
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Acceso en línea:https://doaj.org/article/b7e48c9ffc7642debae4cc5b40151ce5
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spelling oai:doaj.org-article:b7e48c9ffc7642debae4cc5b40151ce52021-11-18T07:53:10ZMonocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.1932-620310.1371/journal.pone.0058791https://doaj.org/article/b7e48c9ffc7642debae4cc5b40151ce52013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23527025/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.Teizo YoshimuraO M Zack HowardToshihiro ItoMasaki KuwabaraAkihiro MatsukawaKeqiang ChenYing LiuMingyong LiuJoost J OppenheimJi Ming WangPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 3, p e58791 (2013)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Teizo Yoshimura
O M Zack Howard
Toshihiro Ito
Masaki Kuwabara
Akihiro Matsukawa
Keqiang Chen
Ying Liu
Mingyong Liu
Joost J Oppenheim
Ji Ming Wang
Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
description MCP-1/CCL2 plays an important role in the initiation and progression of cancer. Since tumor cells produce MCP-1, they are considered to be the main source of this chemokine. Here, we examined whether MCP-1 produced by non-tumor cells affects the growth and lung metastasis of 4T1 breast cancer cells by transplanting them into the mammary pad of WT or MCP-1(-/-) mice. Primary tumors at the injected site grew similarly in both mice; however, lung metastases were markedly reduced in MCP-1(-/-) mice, with significantly longer mouse survival. High levels of MCP-1 mRNA were detected in tumors growing in WT, but not MCP-1(-/-) mice. Serum MCP-1 levels were increased in tumor-bearing WT, but not MCP-1(-/-) mice. Transplantation of MCP-1(-/-) bone marrow cells into WT mice did not alter the incidence of lung metastasis, whereas transplantation of WT bone marrow cells into MCP-1(-/-) mice increased lung metastasis. The primary tumors of MCP-1(-/-) mice consistently developed necrosis earlier than those of WT mice and showed decreased infiltration by macrophages and reduced angiogenesis. Interestingly, 4T1 cells that metastasized to the lung constitutively expressed elevated levels of MCP-1, and intravenous injection of 4T1 cells producing a high level of MCP-1 resulted in increased tumor foci in the lung of WT and MCP-1(-/-) mice. Thus, stromal cell-derived MCP-1 in the primary tumors promotes lung metastasis of 4T1 cells, but tumor cell-derived MCP-1 can also contribute once tumor cells enter the circulation. A greater understanding of the source and role of this chemokine may lead to novel strategies for cancer treatment.
format article
author Teizo Yoshimura
O M Zack Howard
Toshihiro Ito
Masaki Kuwabara
Akihiro Matsukawa
Keqiang Chen
Ying Liu
Mingyong Liu
Joost J Oppenheim
Ji Ming Wang
author_facet Teizo Yoshimura
O M Zack Howard
Toshihiro Ito
Masaki Kuwabara
Akihiro Matsukawa
Keqiang Chen
Ying Liu
Mingyong Liu
Joost J Oppenheim
Ji Ming Wang
author_sort Teizo Yoshimura
title Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
title_short Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
title_full Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
title_fullStr Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
title_full_unstemmed Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
title_sort monocyte chemoattractant protein-1/ccl2 produced by stromal cells promotes lung metastasis of 4t1 murine breast cancer cells.
publisher Public Library of Science (PLoS)
publishDate 2013
url https://doaj.org/article/b7e48c9ffc7642debae4cc5b40151ce5
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