BMP6-induced modulation of the tumor micro-milieu

BMP6-induced modulation of the tumor micro-milieu
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BMP6 诱导的肿瘤微环境调节

DOI:
10.1038/s41388-018-0475-x
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发表时间:
2019
期刊:
影响因子:
8
通讯作者:
Bosserhoff AK
Bosserhoff AK
中科院分区:
医学1区
文献类型:
--
作者:
Stieglitz D;Lamm S;Braig S;Feuerer L;Kuphal S;Dietrich P;Arndt S;Echtenacher B;Hellerbrand C;Karrer S;Bosserhoff AK

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黑色素瘤是最致命的皮肤癌,发病率不断上升,造成严重的健康问题。我们发现骨形态发生蛋白6(BMP6)在黑色素瘤细胞和组织中的表达增加,并观察到BMP6缺乏导致黑色素瘤小鼠模型中肿瘤发病明显延迟和肿瘤进展减慢。此外,我们确定BMP 6抑制真皮肥大细胞募集,并发现肥大细胞衍生的介质在体外显著降低黑色素瘤生长。与此一致,肥大细胞缺乏加速了黑色素瘤小鼠模型中的肿瘤发病和进展。对人黑色素瘤组织的分析揭示了黑色素瘤增殖和肥大细胞浸润之间的强负相关性。这项研究阐明了BMP 6诱导的肿瘤微环境调节的新作用。
Melanoma is the deadliest form of skin cancer with rising incidence, creating a significant health problem. We discovered increased expression of bone morphogenetic protein 6 (BMP6) in melanoma cells and tissues, and observed that BMP6 deficiency caused significantly delayed tumor onset and decelerated tumor progression in a melanoma mouse model. Moreover, we determined that BMP6 inhibits dermal mast cell recruitment and found that mast cell-derived mediators significantly reduced melanoma growth in vitro. In line with this, mast cell deficiency accelerated tumor onset and progression in a melanoma mouse model. Analysis of human melanoma tissues revealed a strong negative correlation between melanoma proliferation and mast cell infiltration. This study elucidates a novel role of BMP6-induced modulation of the tumor microenvironment.
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