Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells
- 127 Downloads
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.
KeywordsBMP signaling BMP-4 Large cell lung carcinoma cell line Live cell imaging Snail
The technical assistance of Cornelia Jörke is greatly acknowledged. We highly appreciate Dr. Mike Fischer for helpful instructions with flow cytometry and Dr. Katrin Hoffmann for support with statistical analysis. We also would like to thank Dr. Christine Gräfe for her helpful support in preparing and paraphrasing this manuscript. JM received a scholarship from the Interdisziplinäres Zentrum für Klinische Forschung (IZKF) Jena. This work was supported in part by Europäische Fonds für regionale Entwicklung-Europa für Thüringen (EFRE, FKZ 2016 FGI 0006).
Compliance with ethical standards
Conflict of interest
All authors declare that they have no conflict of interest.
Human and animal participants
This article does not contain any studies with human participants or animals performed by any of the authors.
- Ferlay J, Ervik M, Lam F, Colombet M, Mery L, Piñeros M, Znaor A, Soerjomataram I, Bray F (2018). Global cancer observatory: cancer today. International Agency for Research on Cancer, Lyon. https://gco.iarc.fr/today. Accessed 14 Feb 2019
- Müller P, Doliva R, Busch M, Philippeit C, Stephan H, Dünker N, Makishima M (2015) Additive effects of retinoic acid (RA) and bone morphogenetic protein 4 (BMP-4) apoptosis signaling in retinoblastoma cell lines. PLoS One 10:1–22Google Scholar