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Secretome of human bone marrow mesenchymal stem cells: an emerging player in lung cancer progression and mechanisms of translation initiation
- Source :
- Tumor Biology. 37:4755-4765
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- Non-small cell lung cancer (NSCLC) remains the most common cause of cancer-related death worldwide. Patients presenting with advanced-stage NSCLC have poor prognosis, while metastatic spread accounts for >70 % of patient's deaths. The major advances in the treatment of lung cancer have brought only minor improvements in survival; therefore, novel strategic treatment approaches are urgently needed. Accumulating data allocate a central role for the cancer microenvironment including mesenchymal stem cells (MSCs) in acquisition of drug resistance and disease relapse. Furthermore, studies indicate that translation initiation factors are over expressed in NSCLC and negatively impact its prognosis. Importantly, translation initiation is highly modulated by microenvironmental cues. Therefore, we decided to examine the effect of bone marrow MSCs (BM-MSCs) from normal donors on NSCLC cell lines with special emphasis on translation initiation mechanism in the crosstalk. We cultured NSCLC cell lines with BM-MSC conditioned media (i.e., secretome) and showed deleterious effects on the cells' proliferation, viability, death, and migration. We also demonstrated reduced levels of translation initiation factors implicated in cancer progression [eukaryotic translation initiation factor 4E (eIF4E) and eukaryotic translation initiation factor 4GI (eIF4GI)], their targets, and regulators. Finally, we outlined a mechanism by which BM-MSCs' secretome affected NSCLC's mitogen-activated protein kinase (MAPK) signaling pathway, downregulated the cell migration, and diminished translation initiation factors' levels. Taken together, our study demonstrates that there is direct dialogue between the BM-MSCs' secretome and NSCLC cells that manipulates translation initiation and critically affects cell fate. We suggest that therapeutic approach that will sabotage this dialogue, especially in the BM microenvironment, may diminish lung cancer metastatic spread and morbidity and improve the patient's life quality.
- Subjects :
- Male
0301 basic medicine
Nucleocytoplasmic Transport Proteins
Lung Neoplasms
Proteome
Cell Survival
Treatment of lung cancer
Bioinformatics
03 medical and health sciences
0302 clinical medicine
Eukaryotic translation
Cell Movement
Carcinoma, Non-Small-Cell Lung
medicine
Humans
Initiation factor
Peptide Chain Initiation, Translational
Lung cancer
Aged
Cell Proliferation
business.industry
Mesenchymal stem cell
EIF4E
Mesenchymal Stem Cells
Cell migration
General Medicine
medicine.disease
030104 developmental biology
medicine.anatomical_structure
030220 oncology & carcinogenesis
Disease Progression
Neoplastic Stem Cells
Cancer research
Female
Bone marrow
Mitogen-Activated Protein Kinases
Eukaryotic Initiation Factor-4G
business
Subjects
Details
- ISSN :
- 14230380 and 10104283
- Volume :
- 37
- Database :
- OpenAIRE
- Journal :
- Tumor Biology
- Accession number :
- edsair.doi.dedup.....c976ec6c913263ee59a7bdbed72bee5c