Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene
Suppression of tumor development and metastasis formation in mice lacking the S100A4(mts1) gene
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DOI：
10.1158/0008-5472.can-04-4510
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发表时间：
2005-05-01
期刊：
影响因子：
11.2
通讯作者：
Ambartsumian, N
中科院分区：
文献类型：
--
作者：
Grum-Schwensen, B;Klingelhofer, J;Ambartsumian, N
S100A4（mts1）蛋白刺激肿瘤细胞的转移扩散。在许多人类癌症中，S100A4的高表达与不良预后相关。利用高度转移性的小鼠乳腺癌细胞CSML100移植，在S100A4缺陷型小鼠中研究了肿瘤发展的动态。与野生型对照相比，在S100A4（-/-）小鼠中观察到肿瘤摄取显著延迟且肿瘤发生率降低。此外，在S100A4（-/-）小鼠中形成的肿瘤从不发生转移。对这些肿瘤的免疫组织化学分析显示血管减少以及宿主来源的基质细胞分布异常。将CSML100细胞与永生化的S100A4（+/+）成纤维细胞共同注射，部分恢复了肿瘤发展的动态以及形成转移的能力。与S100A4（-/-）成纤维细胞相比，这些成纤维细胞的特点是运动性和侵袭性增强，以及具有将S100A4释放到肿瘤环境中的能力。综上所述，我们的结果表明表达S100A4的宿主来源的基质细胞在肿瘤进展和转移中起决定性作用。
The S100A4(mtsl) protein stimulates metastatic spread of tumor cells. An elevated expression of S10OA4 is associated with poor prognosis in many human cancers. Dynamics of tumor development were studied in S100A4-deficient mice using grafts of CSML100, highly metastatic mouse mammary carcinoma cells. A significant delay in tumor uptake and decreased tumor incidences were observed in S10OA4(-/-) mice compared with the wild-type controls. Moreover, tumors developed in S10OA4(-/-) mice never metastasize. Immunohistochemical analyses of these tumors revealed reduced vascularity and abnormal distribution of host-derived stroma cells. Coinjection of CSML100 cells with immortalized S10OA4(+/+) fibroblasts partially restored the dynamics of tumor development and the ability to form metastasis. These fibroblasts were characterized by an enhanced motility and invasiveness in comparison with S10OA4(-/-) fibroblasts, as well as by the ability to release S10OA4 into the tumor environment. Taken together, our results point to a determinative role of host-derived stroma cells expressing S100A4 in tumor progression and metastasis.