Nature Communications:中山大学揭示膀胱癌淋巴转移关键分子机制

2018-10-23 朱汉斌 林伟吟 刘文 科学网

近日,中山大学孙逸仙纪念医院教授林天歆团队揭示了膀胱癌转移的新机制并鉴定出VEGF-C抗体治疗的预测标记物。相关研究成果9月20日发表在《自然—通讯》(Nature Communications)上。林天歆表示,该研究为膀胱癌淋巴转移提供系统性的解决策略。


近日,中山大学孙逸仙纪念医院教授林天歆团队揭示了膀胱癌转移的新机制并鉴定出VEGF-C抗体治疗的预测标记物。相关研究成果9月20日发表在《自然—通讯》(Nature Communications)上。林天歆表示,该研究为膀胱癌淋巴转移提供系统性的解决策略。

膀胱癌是我国泌尿男生殖系统最常见的恶性肿瘤,其致死的主要原因是转移,而淋巴转移是主要和首发的方式。一旦发生淋巴转移,5 年生存率只有25-35%。因此,阐明膀胱癌淋巴转移的分子机制,寻找特异性干预靶点及靶向治疗的预测生物标记物,是膀胱癌研究最为基础和重要的领域。

林天歆团队长期致力于膀胱癌淋巴转移的表观遗传学调控研究,前期实验通过高通量测序鉴定了多个膀胱癌淋巴转移相关的长链非编码RNA(lnc-LBCS)。其中lncRNA-BLACAT2可通过与WDR5结合,调控膀胱癌细胞分泌VEGF-C促进淋巴管新生导致淋巴转移。但是有部分低表达 BLACAT2 的膀胱癌患者也能发生淋巴转移,这提示其他lncRNAs可能通过不同的机制调控淋巴转移。

研究人员首先鉴定了调控膀胱癌肿瘤微环境相关的长链非编码RNA LNMAT1。LNMAT1能够促进肿瘤细胞分泌趋化因子CCL2,进而募集TAMs到膀胱癌肿瘤微环境中。被“引诱”而来的TAMs能够分泌参与膀胱癌淋巴管生成过程的VEGF-C,帮助肿瘤细胞发生淋巴转移。如果能介导到肿瘤微环境这片“土壤”,干预膀胱癌“帮凶”LNMAT1的表达,将能改变“种子”的生存情况,对抑制膀胱癌的进展、改善患者的生存预后发挥重要价值。

据了解,林天歆是2018年国家杰出青年基金获得者。其团队首次阐明LNMAT1通过诱导CCL2募集TAMs促进膀胱癌淋巴转移的关键分子机制,揭示LNMAT1介导肿瘤微环境的重要作用及通过与趋化因子CCL2协同调控TAMs的分子机理。该研究对于在膀胱癌淋巴转移中潜在治疗靶点的临床干预具有重要意义。

原始出处:

Changhao Chen,et.LNMAT1 promotes lymphatic metastasis of bladder cancer via CCL2 dependent macrophage recruitment.Nature Communicationsvolume 9, Article number: 3826 (2018) 

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    2019-02-16 liuli5079
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    2019-10-04 liye789132251

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