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ID 53992
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Author
Yoshimura, Teizo
Howard, O. M. Zack
Ito, Toshihiro
Kuwabara, Masaki
Matsukawa, Akihiro ORCID Kaken ID researchmap
Chen, Keqiang
Liu, Ying
Liu, Mingyong
Oppenheim, Joost J.
Wang, Ji Ming
Abstract
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.
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This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication.
Published Date
2013-03-18
Publication Title
PLOS ONE
Volume
volume8
Issue
issue3
Publisher
PUBLIC LIBRARY SCIENCE
Start Page
e58791
ISSN
1932-6203
Content Type
Journal Article
Official Url
http://dx.doi.org/10.1371/journal.pone.0058791
language
英語
File Version
publisher
Refereed
True
DOI
PubMed ID
Web of Science KeyUT