Author of

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  P2.04 - Poster Session/ Biology, Pathology, and Molecular Testing (ID 234)

  • Event: WCLC 2015
  • Type: Poster
  • Track: Biology, Pathology, and Molecular Testing
  • Presentations: 1
  • Moderators:
  • Coordinates: 9/08/2015, 09:30 - 17:00, Exhibit Hall (Hall B+C)

  • 14553

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    P2.04-063 - Secretome of BM Mesenchymal Stem Cells: An Emerging Player in NSCLC Progression (ID 190)

    09:30 - 09:30  |  Author(s): O. Attar-Schneider
    • Abstract
    • Slides

    Background:
    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 patients deaths. The major advances in 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. Several studies that investigate MSCs in the lung cancer microenvironment revealed that they exhibit genetic and functional abnormalities compared to their normal counterparts. 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 BM-MSCs from normal donors on NSCLC cell lines with special emphasis on the role of translation initiation in the crosstalk.
    
    Methods:
    BM samples were obtained from femur head BM samples of normal donors. NSCLC cell lines (H1299, H460) were treated with BM-MSCs' conditioned medium (i.e secretome) for 72 hours after which NSCLC cells were harvested and assesed for changes in the cells' viability, proliferation/ death, and migration. The cells' were immunoblotted for the levels of translation initiation factors (eIF4E, eIF4GI), their targets, and regulators.
    
    Results:
    Our results demonstarted deleterious effects on the cells’ proliferation, viability, death and migration. We also demonstrated reduced levels of translation initiation factors implicated in cancer progression eIF4E and eIF4GI, their targets, and regulators. Finally, we outlined a mechanism by which BM-MSCs' secretome affected NSCLC's MAPK signaling pathway, downredulated the cells' migration and diminshed translation initiation factors' levles.
    
    Conclusion:
    Our study investigates the effects of microenvironmental cues on NSCLC cells’ fate and critical translation factors that regulate the cells’ tumorigenesis. We showed that there is direct dialogue between the BM-MSCs’ secretome and NSCLC cells that manipulates translation initiation and critically affects cell fate. We showed inhibitory effect on the lung cancer cells’ migration that is regulated both by MAPK signaling pathways and by translation initiation mechanism. Understanding the molecular events which promote metastasis and improving the means of foretelling their development is a major goal of current clinical research. We suggest that theraputic approach that will sabotage this dialoge, espacially in the BM microenviornment, may diminish lung cancer metastatic spread and morbidity and improve the patients life quality. Figure 1
    
    
    
    

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