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瘤生态系统中的动态相互作用:肝瘤细胞和纤维细胞之间的通信

Gábor Petővári¹, Gábor Tóth², Lilla Turiák²

¹Department of Pathology and Experimental Cancer Research, Semmelweis University, Üllői út 26, H-1085 Budapest, Hungary.

International journal of molecular sciences

|September 28, 2023

概括

根据瘤类型,癌细胞和纤维细胞的沟通方式不同. 这种相互作用会影响瘤的进展,并有可能通过特定的microRNAs进行早期肝癌诊断.

科学领域:

癌症生物学癌症生物学
蜂通信蜂通信
瘤微环境瘤微环境

背景情况:

瘤是复杂的生态系统,涉及癌细胞和癌症相关纤维细胞 (CAFs) 等 stromal 细胞.
癌细胞和CAF之间的相互作用对瘤进展至关重要,并且可以根据癌症类型而异.

研究的目的:

研究差分化 (HLE) 和差分化 (HuH7) 肝瘤细胞和LX2纤维细胞之间的通信动态.
探索各种通信途径,包括可溶性因子,代谢物,细胞外囊泡 (EVs) 和微RNA (miRNAs).

主要方法:

肝瘤细胞系 (HLE,HuH7) 与LX2纤维细胞的共同培养系统.
对细胞外矩阵组件,整体表达,矩阵金属蛋白酶 (MMP) 活性和信号通路激活 (MAPK,Wnt) 的分析.
细胞外囊泡 (EV) 和它们的miRNA载荷的特征.

主要成果:

HLE/LX2共同培养导致了拉米林β1,原IV,CD44和syndecan-1脱落的增加;HuH7/LX2共同培养显示出主导的纤维素蛋白,血素-1,原IV和细胞表面syndecan-1.
基于肝瘤细胞分化的基础上观察到差异性整合素和MMP表达.
肝瘤细胞和LX2纤维细胞之间通过直接接触和EV发生了MAPK和Wnt信号的相互激活;LX2衍生的EV在肝瘤EV中调节了SPOCK1.
在肝瘤EV中确定了肝癌特异的miRNAs.

结论:

肝瘤细胞分化决定了与纤维细胞的特定通信模式,影响瘤微环境.
电子电路介导的通信在调节癌细胞和纤维细胞之间的信号通路和货物交换方面发挥着重要作用.
在EV中鉴定出特定于肝癌的miRNA可能具有早期癌症诊断的潜力,需要进一步调查.

关键词:

细胞通信的细胞通信.细胞外囊泡细胞外囊泡纤维细胞细胞是什么?肝癌细胞肝瘤的细胞这是入侵的入侵.代谢代谢代谢代谢这是一个小RNARNA.肌肉干支 (Stroma) 是一种干支.瘤是一个瘤.

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