Acute wounds accelerate tumorigenesis by a T cell-dependent mechanism
Acute wounds accelerate tumorigenesis by a T cell-dependent mechanism
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DOI：
10.1158/0008-5472.can-08-1842
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发表时间：
2008-09-15
期刊：
影响因子：
11.2
通讯作者：
Niederhuber, John E.
中科院分区：
文献类型：
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作者：
Stuelten, Christina H.;Barbul, Adrian;Niederhuber, John E.
我们在同基因小鼠乳腺癌模型中研究了急性损伤对肿瘤生长的影响。将转移性小鼠乳腺癌细胞（4T1）原位注射到 BALB/c 小鼠的乳腺脂肪垫中，并在 9 天后通过乳腺脂肪垫上方或肩胛骨上方的全层真皮切口对动物进行局部损伤。与假治疗相比，局部而非远程损伤增加了肿瘤的大小。在肿瘤部位附近注射伤口液会增加肿瘤的生长，而体外伤口液与血清相比会增加4T1细胞的增殖率。我们的结果表明，伤口基质会对附近肿瘤的生长产生不利影响。这种效应是 T 细胞依赖性的，因为局部受伤对 nu/nu 小鼠的肿瘤生长没有影响。无细胞伤口液可以模拟创伤对肿瘤生长的影响，这表明 T 细胞分泌或介导细胞因子或生长因子的分泌，从而加速肿瘤生长。在这里，我们定义了伤口促进肿瘤生长的实验模型，这将使我们能够确定机制和治疗靶点，以减少组织修复对残留肿瘤的负面影响。
We investigated the influence of acute wounding on tumor growth in a syngeneic mouse breast cancer model. Metastatic mouse breast cancer cells (4T1) were orthotopically injected into the mammary fat pads of BALB/c mice, and animals were wounded locally by full thickness dermal incisions above the mammary fat pads or remotely above the scapula 9 days later. Local, but not remote, wounding increased tumor size when compared with sham treatment. Injection of wound fluid close to the tumor site increased tumor growth, whereas in vitro wound fluid compared with serum increased the proliferation rate of 4T1 cells. Our results show that wound stroma can unfavorably influence growth of nearby tumors. This effect is T cell-dependent, as local wounding had no effect on tumor growth in nu/nu mice. The effect of wounding on tumor growth can be mimicked by acellular wound fluid, suggesting that T cells secrete or mediate secretion of cytokines or growth factors that then accelerate tumor growth. Here, we define an experimental model of wound-promoted tumor growth that will enable us to identify mechanisms and therapeutic targets to reduce the negative effect of tissue repair on residual tumors.