Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells

Inhibition of bone morphogenetic protein signaling reduces viability, growth and migratory potential of non-small cell lung carcinoma cells

Purpose 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...

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Bibliographic Details
Published in:Journal of cancer research and clinical oncology Vol. 145; no. 11; pp. 2675 - 2687
Main Authors: Mihajlović, Jelena, Diehl, Laura A. M., Hochhaus, Andreas, Clement, Joachim H.
Format: Journal Article
Language:English
Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-11-2019
Springer Nature B.V
Subjects:
Aneuploidy
Apoptosis
Bone morphogenetic protein 4
Cancer Research
Cell adhesion & migration
Cell culture
Cell death
Cell migration
Cell proliferation
Cell viability
Down-regulation
Flow cytometry
Gene expression
Gene regulation
Giant cells
Hematology
Internal Medicine
Kinases
Lung cancer
Lung carcinoma
Medicine
Medicine & Public Health
Mesenchyme
Molecular modelling
Non-small cell lung carcinoma
Oncology
Original Article – Cancer Research
Small cell lung carcinoma
Therapeutic applications
Transcription factors
Wound healing
BMP signaling
Large cell lung carcinoma cell line
BMP-4
Snail
Live cell imaging
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Summary:Purpose 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. Methods 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. Results 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. Conclusions 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.
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ISSN:0171-5216
1432-1335
DOI:10.1007/s00432-019-03026-7