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CXCL14/BRAK转基因小鼠中癌发生抑制率以及肿瘤体积和肺转移的降低。

Suppressed rate of carcinogenesis and decreases in tumour volume and lung metastasis in CXCL14/BRAK transgenic mice.

作者信息

Hata Ryu-Ichiro, Izukuri Kazuhito, Kato Yasumasa, Sasaki Soichiro, Mukaida Naofumi, Maehata Yojiro, Miyamoto Chihiro, Akasaka Tetsu, Yang Xiaoyan, Nagashima Yoji, Takeda Kazuyoshi, Kiyono Tohru, Taniguchi Masaru

机构信息

1] Oral Health Science Research Center, Graduate School of Kanagawa Dental University, Yokosuka. 238-8580, Japan [2] Department of Oral Science, Graduate School of Kanagawa Dental University, Yokosuka. 238-8580, Japan.

Department of Oral Function and Molecular Biology, Ohu University School of Dentistry, Koriyama. 963-8611, Japan.

出版信息

Sci Rep. 2015 Mar 13;5:9083. doi: 10.1038/srep09083.

Abstract

Cancer progression involves carcinogenesis, an increase in tumour size, and metastasis. Here, we investigated the effect of overexpressed CXC chemokine ligand 14 (CXCL14) on these processes by using CXCL14/BRAK (CXCL14) transgenic (Tg) mice. The rate of AOM/DSS-induced colorectal carcinogenesis in these mice was significantly lower compared with that for isogenic wild type C57BL/6 (Wt) mice. When tumour cells were injected into these mice, the size of the tumours that developed and the number of metastatic nodules in the lungs of the animals were always significantly lower in the Tg mice than in the Wt ones. Injection of anti-asialo-GM1 antibodies to the mice before and after injection of tumour cells attenuated the suppressing effects of CXCL14 on the tumor growth and metastasis, suggesting that NK cell activity played an important role during CXCL14-mediated suppression of tumour growth and metastasis. The importance of NK cells on the metastasis was also supported when CXCL14 was expressed in B16 melanoma cells. Further, the survival rates after tumour cell injection were significantly increased for the Tg mice. As these Tg mice showed no obvious abnormality, we propose that CXCL14 to be a promising molecular target for cancer suppression/prevention.

摘要

癌症进展涉及致癌作用、肿瘤大小增加和转移。在此,我们通过使用CXCL14/BRAK(CXCL14)转基因(Tg)小鼠研究了过表达的CXC趋化因子配体14(CXCL14)对这些过程的影响。与同基因野生型C57BL/6(Wt)小鼠相比,这些小鼠中AOM/DSS诱导的结直肠癌发生速率显著更低。当将肿瘤细胞注射到这些小鼠体内时,Tg小鼠体内形成的肿瘤大小以及动物肺部转移结节的数量总是显著低于Wt小鼠。在注射肿瘤细胞之前和之后向小鼠注射抗去唾液酸GM1抗体减弱了CXCL14对肿瘤生长和转移的抑制作用,这表明自然杀伤(NK)细胞活性在CXCL14介导的肿瘤生长和转移抑制过程中发挥了重要作用。当CXCL14在B16黑色素瘤细胞中表达时,NK细胞对转移的重要性也得到了证实。此外,Tg小鼠在注射肿瘤细胞后的存活率显著提高。由于这些Tg小鼠未表现出明显异常,我们提出CXCL14是癌症抑制/预防的一个有前景的分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e4c4/4357995/ddd632e5fea9/srep09083-f1.jpg

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