矩阵刚度和肝细胞生长因子对脱细胞化细胞外矩阵基水凝中小细胞肺癌细胞的影响
Yoobin Han1, Chang Seok Ki1,2
1Department of Agriculture, Forestry and Bioresources, Seoul National University, Seoul, 08826, Republic of Korea.
Macromolecular bioscience
|October 25, 2023
概括
这项研究使用3D矩阵重建了小细胞肺癌 (SCLC) 瘤微环境. 研究结果表明,矩阵刚度会影响SCLC细胞的行为和耐药性.
科学领域:
- 生物材料科学 生物材料科学
- 癌症生物学 癌症生物学
- 组织工程是组织工程.
背景情况:
- 小细胞肺癌 (SCLC) 的预后不好,对其3D微环境的理解有限.
- 目前的治疗主要依赖于化疗,但3D矩阵中的SCLC细胞行为尚未得到充分探索.
研究的目的:
- 使用脱细胞化外细胞矩阵 (dECM) 重建SCLC的3D瘤微环境.
- 调查矩阵刚度对SCLC细胞增殖,干细胞,入侵和化学抵抗的影响.
主要方法:
- 从脱细胞化猪肺ECM和氨酸开发了一个基于dECM的水凝.
- 经过修改的dECM和含有甲基酸基团的氨酸用于照相交联,以控制矩阵刚度.
- 在水凝内封装的SCLC细胞,并用肝细胞生长因子 (HGF) 处理.
主要成果:
- 水凝的硬度可以通过不同的dECM含量来调整,模仿正常和癌症组织的硬度.
- 符合标准的水凝 (类似于正常组织) 促进了SCLC细胞的增殖和癌症干细胞标志物的表达.
- 在3D矩阵中,HGF治疗增加了SCLC细胞入侵,CD44和Sox2基因表达,以及对西斯和帕克利塔塞尔的耐药性.
结论:
- 基于肺部dECM的3D矩阵可以有效地重复恶性SCLC行为.
- 矩阵刚度和HGF信号传递在SCLC进展和治疗耐药性方面发挥着关键作用.
- 该模型为在更具生理相关性的微环境中研究SCLC提供了一个平台.
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