Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma.
Crosstalk between Tumor Cells and Macrophages in Stroma Renders Tumor Cells as the Primary Source of MCP-1/CCL2 in Lewis Lung Carcinoma.
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DOI：
10.3389/fimmu.2015.00332
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发表时间：
2015
影响因子：
7.3
通讯作者：
Wang JM
中科院分区：
文献类型：
--
作者：
Yoshimura T;Liu M;Chen X;Li L;Wang JM
趋化因子MCP-1/CCL 2由多种肿瘤产生，在癌症进展中起重要作用。我们和其他人先前证明，MCP-1在几种小鼠肿瘤，包括4 T1乳腺癌，M5076肉瘤和B16黑色素瘤的主要来源是基质细胞。在本研究中，我们确定肿瘤细胞是刘易斯肺癌（LLC）中MCP-1的主要来源，因为MCP-1 mRNA在野生型（WT）和MCP-1−/−小鼠中生长的肿瘤中高度表达，血清MCP-1水平升高。由于从肿瘤中分离的LLC细胞在体外表达低水平的MCP-1，因此似乎肿瘤微环境中的肿瘤-基质细胞相互作用增加了LLC细胞中的MCP-1表达。事实上，LLC细胞与正常小鼠腹腔巨噬细胞或含有巨噬细胞的正常肺细胞的共培养增加了LLC细胞的MCP-1表达。来自TNFα−/−小鼠的巨噬细胞不能激活LLC细胞，抗TNF α中和抗体消除了WT巨噬细胞对LLC细胞的作用。当LLC细胞移植到TNFα−/−小鼠中时，肿瘤中MCP-1 mRNA水平和血清MCP-1水平与WT小鼠相比明显降低，重要的是，肿瘤生长更慢。总之，我们的结果表明，肿瘤细胞激活的巨噬细胞释放的TNFα对肿瘤细胞增加MCP-1的产生至关重要。因此，肿瘤-基质细胞相互作用的破坏可以通过减少促肿瘤促炎介质如MCP-1的产生来抑制肿瘤进展。
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.
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影响因子：
8.8
作者：
Hirose, K.;Hakozaki, M.;Nyunoya, Y.;Kobayashi, Y.;Matsushita, K.;Takenouchi, T.;Mikata, A.;Mukaida, N.;Matsushima, K.
通讯作者：
Matsushima, K.
影响因子：
82.9
作者：
Moore, RJ;Owens, DM;Balkwill, F
通讯作者：
Balkwill, F
影响因子：
11.2
作者：
Lu, Yi;Cai, Zhong;Zhang, Jian
通讯作者：
Zhang, Jian
影响因子：
3
作者：
Clausen, BE;Burkhardt, C;Förster, I
通讯作者：
Förster, I
影响因子：
9.7
作者：
BERTRAM, JS;JANIK, P
通讯作者：
JANIK, P