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在PDPN/CCL2/STAT3反循环中,改变CAF异质性以促进结直肠癌中的血管生成

Die Yu^1,2, Hanzheng Xu^1,2, Jinzhe Zhou³

¹State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, East China University of Science and Technology, 130 Meilong Rd, Shanghai, 200237, China.

|August 8, 2024

概括

结肠直肠癌 (CRC) 血管生成是由异质的癌症相关纤维细胞 (CAF) 驱动的. 波多普拉宁 (PDPN) + CAFs通过PDPN/CCL2/STAT3循环促进这种作用,提供治疗点.

科学领域:

在瘤学瘤学.
癌症生物学癌症生物学
分子医学是分子医学.

背景情况:

结肠直肠癌 (CRC) 是全球癌症死亡的主要原因.
瘤微环境 (TME),特别是与癌症相关的纤维细胞 (CAF),显著影响瘤的进展,包括血管新生.
CAF的异质性使理解它们在促进瘤血管生成中的作用变得复杂.

研究的目的:

为了研究CAFs在结直肠癌中的功能异质性.
为了确定亲血管性CAF亚群的特定标记物.
阐明CAFs在CRC中促进血管生成的分子机制.

主要方法:

在CRC中CAF亚种群的表征.
鉴定波多普拉宁 (PDPN) 作为亲血管性CAF的标记物.
在CAF和内皮细胞中分析PDPN/CCL2/STAT3信号轴.
评估WP1066作为CRC血管生成的抑制剂.

主要成果:

在结直肠癌中的CAF中证明了亲血管性功能异质性.
确定PDPN作为具有亲血管功能的CAF的特定标志物.
透露PDPN+CAF通过自克林PDPN/CCL2/STAT3反循环保持异质性.
表明CAFs通过帕克林CCL2通过STAT3通路对内皮细胞起作用来促进血管生成.
通过破坏CAF内在和内皮细胞信号传递,WP1066有效地抑制了CRC血管生成.

结论:

在结直肠癌中,STAT3信号传递是CAF驱动的血管生成的关键调解者.
在PDPN+CAF中,PDPN+CAF代表了一个可向的亲血管性亚群.
在内皮细胞中准PDPN/CCL2/STAT3轴和STAT3为CRC提供了双重治疗策略.
WP1066显示出作为一种新型治疗剂的潜力,可以抑制结直肠癌血管生成.

关键词:

血管新生的产生.在 CAF 中,CAF 是 CAF.在CRC中,CRC就是CRC.在PDPN中使用PDPN.在STAT3中,我们可以使用STAT3.

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