Tumour biology and pathology

9P - Mesenchymal stem cells’ microvesicles from primary and metastatic NSCLC niches differentially modulate lung cancer cells

Authors
  • Oshrat Attar-Schneider (IL)
  • Liat Drucker (IL)
  • Maya Gottfried (IL)
Presenter
  • Oshrat Attar-Schneider (IL)

Abstract

Background

Novel therapeutic approaches are urgently needed in lung cancer, particularly ones that address the malignant cells in their stroma microenvironment critical to drug resistance and disease relapse. The stroma constituents, mesenchymal stem cells (MSCs), interact with cancer cells by various methods including transfer of microvesicles (MVs) that vehicle protein, mRNA and microRNAs thereby altering recipient cells’ phenotype. Here, we examined the effect of MSCs’ MVs from primary (lung) and metastatic (bone marrow (BM)) niches on NSCLC cells with emphasis on translation initiation's (TI) role in the process.

Methods

Lung and BM MSCs’ MVs were isolated and applied to NSCLC cell lines (H1299, H460). MVs uptake was confirmed and NSCLC cells were assayed for: viability (WST-1); cell count/death (trypan); proliferation (PCNA); migration (scratch); autophagy; TI status (factors, regulators, targets); MAPKs activation (immunoblotting).

Results

We observed increased viability, proliferation and migration of Lung-MSCs’ MVs treated NSCLC cells whereas, BM-MSCs’ MVs treated cells showed reductions (50–90% and −40%, respectively p < 0.05). Correspondingly, Lung MSCs’ MVs elevated TI status whereas BM-MSCs’ MVs diminished it (60–120% and −30–70%, respectively p < 0.05). The opposite trend was also evident in MAPK activation and autophagy induction.

Conclusions

Our observations not only depict a role for MSCs’ MVs in NSCLC phenotype but also display distinct differences between the primary and metastatic niches and may emphasize specific factors that shape disease progression. Further studies into the mechanism underlying the MVs-NSCLC cells’ contact and cargo transfer may promote the design of a therapeutic approach that will sabotage the dialogue between NSCLC cells and MSCs.

Legal entity responsible for the study

Meir Medical Center

Funding

Has not received any funding

Disclosure

All authors have declared no conflicts of interest.

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