科学家发现乳腺癌从淋巴结转移新机制

　　对于几乎所有癌症，淋巴结转移都与预后较差相关，但是癌细胞能否直接从淋巴结转移仍然存在争议。此外，癌细胞如何生存于淋巴结并且离开的具体机制尚不明确。

　　2019年9月13日，英国《自然》旗下《自然通讯》发表美国北卡罗来纳大学教堂山分校、莱恩伯格综合癌症中心的研究报告，发现了乳腺癌从淋巴结转移的新机制。

　　该研究表明，乳腺癌患者经常发生类似远处转移的淋巴结转移。此外，显微手术模型表明，染色质修饰基因通过表达组蛋白脱乙酰酶11可以调节淋巴结转移的发生和扩散。通过基因手段或奎诺司他、伏林司他、恩替司他等药物阻断组蛋白脱乙酰酶11，可以减少淋巴结转移癌细胞的生长，但是也显著增加了癌细胞的迁移和远处转移形成。

　　因此，该研究结果表明，组蛋白脱乙酰酶11即可抑制乳腺癌生长，又可促进乳腺癌从淋巴结转移，故组蛋白脱乙酰酶抑制剂用药时需要谨慎。

Nat Commun. 2019 Sep 13;10(1):4182.

Histone deacetylase 11 inhibition promotes breast cancer metastasis from lymph nodes.

Leslie PL, Chao YL, Tsai YH, Ghosh SK, Porrello A, Van Swearingen AED, Harrison EB, Cooley BC, Parker JS, Carey LA, Pecot CV.

UNC Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, NC, USA.

Lymph node (LN) metastases correspond with a worse prognosis in nearly all cancers, yet the occurrence of cancer spreading from LNs remains controversial. Additionally, the mechanisms explaining how cancers survive and exit LNs are largely unknown. Here, we show that breast cancer patients frequently have LN metastases that closely resemble distant metastases. In addition, using a microsurgical model, we show how LN metastasis development and dissemination is regulated by the expression of a chromatin modifier, histone deacetylase 11 (HDAC11). Genetic and pharmacologic blockade of HDAC11 decreases LN tumor growth, yet substantially increases migration and distant metastasis formation. Collectively, we reveal a mechanism explaining how HDAC11 plasticity promotes breast cancer growth as well as dissemination from LNs and suggest caution with the use of HDAC inhibitors.

PMID: 31519896

DOI: 10.1038/s41467-019-12222-5