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骨形态发生蛋白信号传导是卵巢癌的一个治疗靶点。

BMP signaling is a therapeutic target in ovarian cancer.

作者信息

Fukuda Tomohiko, Fukuda Risa, Tanabe Ryo, Koinuma Daizo, Koyama Hiroo, Hashizume Yoshinobu, Moustakas Aristidis, Miyazono Kohei, Heldin Carl-Henrik

机构信息

Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Box 582, Uppsala University, SE-751 23, Uppsala, Sweden.

Department of Molecular Pathology, Graduate School of Medicine, The University of Tokyo, Hongo 7-3-1 Bunkyo-ku, Tokyo, 113-8655, Japan.

出版信息

Cell Death Discov. 2020 Dec 5;6(1):139. doi: 10.1038/s41420-020-00377-w.

DOI:10.1038/s41420-020-00377-w
PMID:33298901
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7719168/
Abstract

BMP signaling has been found to have tumor-promoting as well as tumor-suppressing effects in different types of tumors. In this study, we investigated the effects of BMP signaling and of BMP inhibitors on ovarian cancer (OC) cells in vitro and in vivo. High expression of BMP receptor 2 (BMPR2) correlated with poor overall survival of OC patients in the TCGA dataset. Both BMP2 and BMPR2 enhanced OC cell proliferation, whereas BMP receptor kinase inhibitors inhibited OC cell growth in cell culture as well as in a mouse model. BMP2 also augmented sphere formation, migration, and invasion of OC cells, and induced EMT. High BMP2 expression was observed after chemotherapy of OC patients in the GSE109934 dataset. In accordance, carboplatin, used for the treatment of OC patients, increased BMP2 secretion from OC cells, and induced EMT partially via activation of BMP signaling. Our data suggest that BMP signaling has tumor-promoting effects in OC, and that BMP inhibitors might be useful therapeutic agents for OC patients. Considering that carboplatin treatment augmented BMP2 secretion, the possibility to use a combination of BMP inhibitors and carboplatin in the treatment of OC patients, would be worth exploring.

摘要

已发现骨形态发生蛋白（BMP）信号在不同类型肿瘤中具有促肿瘤和抑肿瘤作用。在本研究中，我们在体外和体内研究了BMP信号及BMP抑制剂对卵巢癌（OC）细胞的影响。在TCGA数据集中，BMP受体2（BMPR2）的高表达与OC患者较差的总生存率相关。BMP2和BMPR2均增强OC细胞增殖，而BMP受体激酶抑制剂在细胞培养以及小鼠模型中均抑制OC细胞生长。BMP2还增强OC细胞的成球、迁移和侵袭能力，并诱导上皮-间质转化（EMT）。在GSE109934数据集中，OC患者化疗后观察到BMP2高表达。相应地，用于治疗OC患者的卡铂增加了OC细胞的BMP2分泌，并部分通过激活BMP信号诱导EMT。我们的数据表明，BMP信号在OC中具有促肿瘤作用，并且BMP抑制剂可能是OC患者有用的治疗药物。考虑到卡铂治疗会增加BMP2分泌，在OC患者治疗中联合使用BMP抑制剂和卡铂的可能性值得探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/c40ca3c163f4/41420_2020_377_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/1ef6df6dd7ea/41420_2020_377_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/2334465377ba/41420_2020_377_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/4d23b55ed4d5/41420_2020_377_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/71e8e02dbbf8/41420_2020_377_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/96c8129329e1/41420_2020_377_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/3cb504ae823c/41420_2020_377_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/c40ca3c163f4/41420_2020_377_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/1ef6df6dd7ea/41420_2020_377_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/2334465377ba/41420_2020_377_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/4d23b55ed4d5/41420_2020_377_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/71e8e02dbbf8/41420_2020_377_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/96c8129329e1/41420_2020_377_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/3cb504ae823c/41420_2020_377_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8291/7719168/c40ca3c163f4/41420_2020_377_Fig7_HTML.jpg

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