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在神经内分泌前列腺癌中准αVβ3/NgR2通路

Anna Testa¹, Fabio Quaglia¹, Nicole M Naranjo¹

¹Prostate Cancer Discovery and Development Program, Thomas Jefferson University, Philadelphia, PA, United States; Department of Pharmacology, Physiology, and Cancer Biology, Thomas Jefferson University, Philadelphia, PA, United States.

Matrix biology : journal of the International Society for Matrix Biology

|November 13, 2023

概括

用LM609抗体向αVβ3整合素可以抑制神经内分泌前列腺癌的生长. 研究人员发现NgR2调节神经内分泌标记物,并在细胞外囊泡中发现αVβ3整合素和NgR2,增强单细胞粘附.

科学领域:

在瘤学瘤学.
细胞生物学细胞生物学
分子医学是分子医学.

背景情况:

神经内分泌前列腺癌 (NEPC) 是具有攻击性,转移性和抗抗雄激素剥夺疗法的,导致预后不佳.
在NEPC中,αVβ3整合素过度表达,因此具有潜在的治疗标.
NgR2,一种新的αVβ3整合素结合伙伴,调节前列腺癌细胞中的神经内分泌分化.

研究的目的:

在NEPC中研究向αVβ3整蛋白的治疗潜力.
阐明ngr2在NEPC进展和细胞粘附中的作用.
来自NEPC患者的细胞外囊泡的功能特征.

主要方法:

在患者衍生异种移植中使用针对αVβ3整体的LM609单克隆抗体.
在体外功能测试以评估ngr2在细胞粘附中的作用.
在患者血中的小细胞外囊中对αVβ3整合素和NgR2的同分离分析.
用患者衍生的细胞外囊泡化人类单细胞.

主要成果:

在体内,LM609治疗阻碍了NEPC患者衍生的异种移植的生长.
发现ngR2对于促进细胞粘附于αVβ3整合素连接体至关重要.
来自NEPC患者血的小细胞外囊中含有αVβ3整合素和NgR2,并增加了单细胞对纤维蛋白的粘附.
暴露在这些囊泡中的单细胞成为"粘附能力",而不会改变传统的极化标记.

结论:

向αVβ3整合素是NEPC的一种有前途的治疗策略.
R2在NEPC细胞粘附和分化中起着重要作用.
来自NEPC的细胞外囊泡调解细胞-细胞通信,可能影响免疫细胞功能.
这些发现为NEPC管理中的诊断和治疗方法提供了新的途径.

关键词:

单细胞 (Monocytes) 是一种单细胞.神经内分泌前列腺癌的前列腺癌.在 NgR2R2 中.患者血中的患者血.小小的细胞外囊泡.在 αVβ3 整体中.

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