凝血因子X在前列腺癌中促进对雄激素缺乏治疗的抵抗力
Bianca Calì1, Martina Troiani1, Silvia Bressan2
1Institute of Oncology Research (IOR), 6500 Bellinzona, Switzerland; Università della Svizzera Italiana, Faculty of Biomedical Sciences, CH6900 Lugano, Switzerland.
前列腺瘤中的中性粒细胞 (PMN-MDSC) 产生凝血因子X (FX),通过PAR2信号驱动癌症生长. 抑制XA因子 (FXa) 会减缓瘤的进展,并增强癌症治疗.
科学领域:
- 在瘤学瘤学.
- 血液学 血液学 血液学
- 分子生物学分子生物学
背景情况:
- 高凝血性与癌症有关,但凝血因子在瘤细胞增殖中的直接作用尚不清楚.
- 抗割前列腺癌 (CRPC) 是一个重大的临床挑战,治疗选择有限.
研究的目的:
- 调查凝血因子在前列腺瘤细胞增殖中的直接作用.
- 在CRPC的瘤微环境 (TME) 中识别新的治疗点.
主要方法:
- 单细胞RNA测序 (scRNA-seq) 的CRPC小鼠模型TME.
- 对Xa因子 (FXa) 的遗传和药理抑制.
- 在人类CRPC患者瘤中分析FX,CD84和PAR2水平.
主要成果:
- 确定PMN-MDSCs是TME中凝血因子X (FX) 的主要肝外来源.
- 激活FX通过激活瘤细胞中的PAR2和ERK1/2来促进瘤的安卓独立生长.
- 抑制FXa降低了瘤进展,并与恩扎胺协同作用;CD84结合增强了F10表达.
结论:
- FXa直接促进前列腺癌的生长和进展.
- FX,CD84和PAR2是CRPC患者生存的潜在生物标志物.
- 准FXa和PMN-MDSC为CRPC提供了一个有前途的治疗策略.
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