Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
Monocyte chemoattractant protein-1/CCL2 produced by stromal cells promotes lung metastasis of 4T1 murine breast cancer cells.
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DOI：
10.1371/journal.pone.0058791
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Wang JM
中科院分区：
文献类型：
--
作者：
Yoshimura T;Howard OM;Ito T;Kuwabara M;Matsukawa A;Chen K;Liu Y;Liu M;Oppenheim JJ;Wang JM
MCP-1/CCL 2在肿瘤的发生和发展中起重要作用。由于肿瘤细胞产生MCP-1，它们被认为是这种趋化因子的主要来源。在这里，我们通过将4 T1乳腺癌细胞移植到WT或MCP-1−/−小鼠的乳腺垫中，研究了由非肿瘤细胞产生的MCP-1是否会影响4 T1乳腺癌细胞的生长和肺转移。两种小鼠注射部位的原发性肿瘤生长相似;然而，MCP-1−/−小鼠的肺转移显著减少，小鼠存活期显著延长。在WT小鼠的肿瘤中检测到高水平的MCP-1 mRNA，但在MCP-1−/−小鼠中未检测到。荷瘤WT小鼠的血清MCP-1水平升高，但MCP-1-/-小鼠的血清MCP-1水平未升高。将MCP-1−/−骨髓细胞移植到WT小鼠中不会改变肺转移的发生率，而将WT骨髓细胞移植到MCP-1−/−小鼠中会增加肺转移。MCP-1−/−小鼠的原发性肿瘤始终比WT小鼠更早发生坏死，并显示巨噬细胞浸润减少和血管生成减少。有趣的是，转移到肺的4 T1细胞组成性表达MCP-1水平升高，静脉注射产生高水平MCP-1的4 T1细胞导致WT和MCP-1−/−小鼠肺中肿瘤灶增加。因此，原发性肿瘤中的基质细胞衍生的MCP-1促进4 T1细胞的肺转移，但是一旦肿瘤细胞进入循环，肿瘤细胞衍生的MCP-1也可以起作用。更好地了解这种趋化因子的来源和作用可能会导致癌症治疗的新策略。
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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影响因子：
50.3
作者：
Granot Z;Henke E;Comen EA;King TA;Norton L;Benezra R
通讯作者：
Benezra R
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
DOI：
10.1161/atvbaha.111.233536
发表时间：
2011-11-01
影响因子：
8.7
作者：
Arderiu, Gemma;Pena, Esther;Badimon, Lina
通讯作者：
Badimon, Lina