Klinik Innere Medizin II, Abteilung Hämatologie und Internistische Onkologie, Universitätsklinikum Jena, Am Klinikum 1, 07747, Jena, Germany.
J Cancer Res Clin Oncol. 2019 Nov;145(11):2675-2687. doi: 10.1007/s00432-019-03026-7. Epub 2019 Sep 17.
BMP signaling has an oncogenic and tumor-suppressing activity in lung cancer that makes the prospective therapeutic utility of BMP signaling in lung cancer treatment complex. A more in-depth analysis of lung cancer subtypes is needed to identify BMP-related therapeutic targets. We sought to examine the influence of BMP signaling on the viability, growth and migration properties of the cell line LCLC-103H, which originates from a large cell lung carcinoma with giant cells and an extended aneuploidy.
We used BMP-4 and LDN-214117 as agonist/antagonist system for the BMP receptor type I signaling. Using flow cytometry, wound healing assay, trans-well assay and spheroid culture, we examined the influence of BMP signaling on cell viability, growth and migration. Molecular mechanisms underlying observed changes in cell migration were investigated via gene expression analysis of epithelial-mesenchymal transition (EMT) markers.
BMP signaling inhibition resulted in LCLC-103H cell apoptosis and necrosis 72 h after LDN-214117 treatment. Cell growth and proliferation are markedly affected by BMP signaling inhibition. Chemotactic motility and migratory ability of LCLC-103H cells were clearly hampered by LDN-214117 treatment. Cell migration changes after BMP signaling inhibition were shown to be coupled with considerable down-regulation of transcription factors involved in EMT, especially Snail.
BMP signaling inhibition in LCLC-103H cells leads to reduced growth and proliferation, hindered migration and accelerated cell death. The findings contribute to the pool of evidence on BMP signaling in lung cancer with a possibility of introducing BMP signaling inhibition as a novel therapeutic approach for the disease.
BMP 信号在肺癌中具有致癌和抑癌活性，这使得 BMP 信号在肺癌治疗中的潜在治疗用途变得复杂。需要更深入地分析肺癌亚型，以确定与 BMP 相关的治疗靶点。我们试图研究 BMP 信号对源自具有巨大细胞和广泛非整倍体的大细胞肺癌的细胞系 LCLC-103H 的活力、生长和迁移特性的影响。
我们使用 BMP-4 和 LDN-214117 作为 BMP 受体 I 信号的激动剂/拮抗剂系统。通过流式细胞术、划痕愈合试验、Transwell 试验和球体培养，我们研究了 BMP 信号对细胞活力、生长和迁移的影响。通过上皮-间充质转化（EMT）标志物的基因表达分析，研究了观察到的细胞迁移变化的分子机制。
BMP 信号抑制导致 LDN-214117 处理 72 小时后 LCLC-103H 细胞凋亡和坏死。BMP 信号抑制明显影响细胞生长和增殖。LDN-214117 处理明显阻碍了 LCLC-103H 细胞的趋化运动和迁移能力。BMP 信号抑制后细胞迁移的变化与 EMT 相关转录因子的显著下调有关，尤其是 Snail。
LCLC-103H 细胞中 BMP 信号抑制导致生长和增殖减少、迁移受阻和细胞死亡加速。这些发现为肺癌中 BMP 信号的研究提供了更多的证据，并有可能将 BMP 信号抑制作为该疾病的一种新的治疗方法。
