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C. Garnis



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    MA02 - RNA in Lung Cancer (ID 377)

    • Event: WCLC 2016
    • Type: Mini Oral Session
    • Track: Biology/Pathology
    • Presentations: 1
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      MA02.01 - Extracellular Vescicle miRNAs Regulate Gene Expression in Local Lung Adenocarcinoma Endothelial Cells (ID 4655)

      14:20 - 14:26  |  Author(s): C. Garnis

      • Abstract
      • Presentation
      • Slides

      Background:
      Extracellular vesicles are small vesicles released from all cell types which can be used as a form of cell to cell communication. Recently these extracellular vesicles have been shown to play a key role in cancer development, growth, progression and angiogenesis. These extracellular vesicles are loaded with functional mRNAs, miRNAs and proteins which can be transferred from one cell to another. Extracellular vesicles have been known to enter neighboring cells including the surrounding stroma, and even enter biofluids. Our research shows that miRNAs transferred from lung adenocarcinoma cells through extracellular vesicles influence gene expression in endothelial cells and enhance their ability to form new blood vessels.

      Methods:
      Using 5 lung adenocarcinoma cell lines (H1395, H1437, H2073, H2228 and H2347) we isolated extracellular vesicles using differential ultracentrifugation. RNA was extracted from the extracellular vesicles as well as the cells from which they were derived and profiled for 742 miRNAs using the miRCURY LNA[TM] Universal RT miRNA PCR system (Exiqon) to identify miRNAs that were enriched by at least 4-fold in the extracellular vesicles. Tube formation assays were conducted on a commonly used endothelial cell line HMEC-1.

      Results:
      We found an enrichment of a select set of miRNAs within lung adenocarcinoma extracellular vesicles. These miRNAs have previously been identified as tumor suppressors: miR-142-3p, miR-143-3p, miR-144-3p, miR-145-5p, miR-150-5p, miR-223-3p, miR-451a, miR-486-5p, miR-605-5p in various cancer types. When extracellular vesicles are isolated from miR-143 and miR-145 over expressing adenocarcinoma lines they contain an increase in their over expressed miRNAs. When these miRNA enriched exosomes were incubated with HMEC-1 cells, we observed an increase in their ability to form new blood vessels and a decrease in the expression of CAMK1D in the endothelial cells. miR-143-3p and miR-145-5p were also found to be enriched in serum samples draining directly from lung adenocarcinoma tumors compared to arterial serum.

      Conclusion:
      Extracellular vesicles originating from lung adenocarcinoma cells can enter into endothelial cells and increase their ability to form new blood vessels through extracellular vesicle transfer of miR-145/miR-143 suggesting that this form of communication increases angiogenesis within lung adenocarcinoma tumors.

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