Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response.
Activin enhances skin tumourigenesis and malignant progression by inducing a pro-tumourigenic immune cell response.
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DOI：
10.1038/ncomms1585
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发表时间：
2011-12-06
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
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作者：
激活素是伤口修复的重要协调者，但其在皮肤癌发生中的潜在作用尚未得到解决。在这里，我们使用不同类型的转基因小鼠，增强皮肤中激活素的水平，通过诱导促肿瘤微环境促进皮肤肿瘤形成及其恶性进展。这包括表皮中促肿瘤朗格汉斯细胞和调节性T细胞的积累。此外，激活素抑制肿瘤抑制性表皮γδ T细胞的增殖，导致它们在肿瘤促进期间进行性丧失。与对照组织相比，在人皮肤基底细胞癌和鳞状细胞癌中也发现激活素表达增加。这些发现突出了伤口愈合和癌症之间的相似之处，并表明抑制激活素作用是治疗过度表达该因子的癌症的有希望的策略。 已知激活素在伤口愈合中起作用，但其在皮肤癌中的作用尚不清楚。Antsiferova等人表明，激活素在人类皮肤肿瘤中升高，并且通过调节表皮免疫细胞，加剧了皮肤癌小鼠模型中的肿瘤进展。
Activin is an important orchestrator of wound repair, but its potential role in skin carcinogenesis has not been addressed. Here we show using different types of genetically modified mice that enhanced levels of activin in the skin promote skin tumour formation and their malignant progression through induction of a pro-tumourigenic microenvironment. This includes accumulation of tumour-promoting Langerhans cells and regulatory T cells in the epidermis. Furthermore, activin inhibits proliferation of tumour-suppressive epidermal γδ T cells, resulting in their progressive loss during tumour promotion. An increase in activin expression was also found in human cutaneous basal and squamous cell carcinomas when compared with control tissue. These findings highlight the parallels between wound healing and cancer, and suggest inhibition of activin action as a promising strategy for the treatment of cancers overexpressing this factor. Activin is known to have a role in wound healing, but its role in skin cancer is unknown. Antsiferova et al. show that activin is elevated in human skin tumours, and by modulating epidermal immune cells, exacerbates tumour progression in a mouse model of skin cancer.
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DOI：
10.4049/jimmunol.0902593
发表时间：
2010-04-01
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Jacobs SR;Michalek RD;Rathmell JC
通讯作者：
Rathmell JC
影响因子：
64.8
作者：
AKHURST, RJ;FEE, F;BALMAIN, A
通讯作者：
BALMAIN, A
影响因子：
4.4
作者：
Gawa, Kenji;Funaba, Masayuki;Tsujimoto, Masafumi
通讯作者：
Tsujimoto, Masafumi
影响因子：
14.8
作者：
通讯作者：
--
影响因子：
9.8
作者：
Chang HY;Sneddon JB;Alizadeh AA;Sood R;West RB;Montgomery K;Chi JT;van de Rijn M;Botstein D;Brown PO
通讯作者：
Brown PO