Abstract
The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.
| Original language | English |
|---|---|
| Article number | 332 |
| Journal | Frontiers in Immunology |
| Volume | 6 |
| Issue number | JUN |
| DOIs | |
| Publication status | Published - 2015 |
| Externally published | Yes |
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Keywords
- Chemokines
- Inflammation
- Lung cancer
- Monocytes/macrophages
- Tumor microenvironment
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Crosstalk between tumor cells and macrophages in stroma renders tumor cells as the primary source of MCP-1/CCL2 in Lewis lung carcinoma. / Yoshimura, Teizo; Liu, Mingyong; Chen, Xin; Li, Liangzhu; Wang, Ji Ming.
In: Frontiers in Immunology, Vol. 6, No. JUN, 332, 2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Crosstalk between tumor cells and macrophages in stroma renders tumor cells as the primary source of MCP-1/CCL2 in Lewis lung carcinoma
AU - Yoshimura, Teizo
AU - Liu, Mingyong
AU - Chen, Xin
AU - Li, Liangzhu
AU - Wang, Ji Ming
PY - 2015
Y1 - 2015
N2 - The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.
AB - The chemokine MCP-1/CCL2 is produced by a variety of tumors and plays an important role in cancer progression. We and others previously demonstrated that the primary source of MCP-1 in several mouse tumors, including 4T1 breast cancer, M5076 sarcoma, and B16 melanoma, was stromal cells. In the present study, we identified that tumor cells were the primary source of MCP-1 in Lewis lung carcinoma (LLC), because MCP-1 mRNA was highly expressed in tumors grown in both wild type (WT) and MCP-1-/- mice with elevated serum MCP-1 levels. Since LLC cells isolated from tumors expressed low levels of MCP-1 in vitro, it appeared that the tumor-stromal cell interaction in a tumor microenvironment increased MCP-1 expression in LLC cells. In fact, co-culture of LLC cells with normal mouse peritoneal macrophages or normal lung cells containing macrophages increased MCP-1 expression by LLC cells. Macrophages from TNFα-/- mice failed to activate LLC cells and anti-TNFα neutralizing antibody abolished the effect of WT macrophages on LLC cells. When LLC cells were transplanted into TNFα-/- mice, the levels of MCP-1 mRNA in tumors and serum MCP-1 levels were markedly lower as compared to WT mice, and importantly, tumors grew more slowly. Taken together, our results indicate that TNFα released by tumor cell-activated macrophages is critical for increased MCP-1 production by tumors cells. Thus, disruption of tumor-stromal cell interaction may inhibit tumor progression by reducing the production of tumor-promoting proinflammatory mediators, such as MCP-1.
KW - Chemokines
KW - Inflammation
KW - Lung cancer
KW - Monocytes/macrophages
KW - Tumor microenvironment
UR - http://www.scopus.com/inward/record.url?scp=84935043372&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84935043372&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2015.00332
DO - 10.3389/fimmu.2015.00332
M3 - Article
AN - SCOPUS:84935043372
VL - 6
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - JUN
M1 - 332
ER -