Institute of Biochemistry, Emil Fischer Center, Department of Biochemistry and Molecular Medicine, University of Erlangen-Nürnberg, Erlangen, Germany.
Department of Pharmacy, Pharmaceutical Biology, University of Munich, Munich, Germany.
Oncogene. 2019 Jan;38(5):609-621. doi: 10.1038/s41388-018-0475-x. Epub 2018 Aug 31.
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.
黑色素瘤是皮肤癌中最致命的一种，发病率不断上升，成为一个严重的健康问题。我们发现黑色素瘤细胞和组织中骨形态发生蛋白 6（BMP6）的表达增加，并观察到 BMP6 缺乏会导致黑色素瘤小鼠模型中的肿瘤发生明显延迟和肿瘤进展减缓。此外，我们确定 BMP6 抑制真皮肥大细胞的募集，并发现肥大细胞衍生的介质显著减少体外黑色素瘤的生长。与此一致的是，肥大细胞缺乏会加速黑色素瘤小鼠模型中的肿瘤发生和进展。对人类黑色素瘤组织的分析显示，黑色素瘤增殖与肥大细胞浸润之间存在强烈的负相关。本研究阐明了 BMP6 诱导的肿瘤微环境调节的新作用。
