瘤和微环境中的MDA-9/Syntenin定义了前列腺癌的骨转移
Santanu Maji1, Anjan K Pradhan1,2, Amit Kumar1
1Department of Human and Molecular Genetics, Virginia Commonwealth University, School of Medicine, Richmond, VA 23298.
概括
黑色素瘤分化相关基因-9 (MDA-9) 通过改变瘤微环境驱动前列腺癌骨转移. 抑制MDA-9可能为晚期前列腺癌提供新的治疗策略.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 癌症转移 癌症转移
背景情况:
- 骨转移是晚期前列腺癌 (PC) 的常见,无法治愈的并发症.
- 转移性利基包括瘤细胞和骨细胞之间的相互作用.
- 黑色素瘤分化关联基因-9 (MDA-9/Syntenin) 是一种被发现在骨髓衍生的介酶体 stromal 细胞 (BM-MSCs) 中的前列转移基因.
研究的目的:
- 调查MDA-9在前列腺癌骨转移中的作用.
- 为了阐明MDA-9在骨微环境中调节的信号通路.
- 为了确定晚期PC骨转移的潜在治疗点.
主要方法:
- 在前列腺癌中使用了mda-9淘汰模式.
- 分析了PDGF-AA,CXCL5,YAP/MST信号的表达.
- 研究了骨转移性利基中的瘤细胞增殖和免疫抑制.
主要成果:
- 来自瘤细胞的PDGF-AA通过抑制MDA-9依赖的YAP/MST信号,诱导BM-MSC中的CXCL5.
- MDA-9/CXCL5轴促进PC细胞的增殖和免疫抑制.
- mda-9淘汰赛瘤细胞显示PDGF-AA减少,没有骨转移的发展.
结论:
- 在调节PC骨转移中,MDA-9/Syntenin在调节PC骨转移方面发挥着至关重要的,以前未被定义的作用.
- MDA-9/CXCL5信号轴是骨中PC进展的关键驱动因素.
- 针对MDA-9提供了一个潜在的翻译策略,用于管理高级PC并发症.
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