Author of

• 12364

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  P3.01 - Poster Session 3 - Cancer Biology (ID 147)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/30/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 12374

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    P3.01-010 - Tumor-derived microvesicles mediate the transfer of gefitinib resistance in lung cancer cells harboring T790M EGFR mutation (ID 1751)

    09:30 - 09:30  |  Author(s): J.Y. Heo
    • Abstract

    Background
    Tumor-derived microvesicles (TMV) contain bioactive molecules including proteins, RNA, microRNA, and DNA, and shed TMV propagate the horizontal transfer of their cargo in tumor microenvironment. TMV play important roles in cancer biology such as tumor progression, angiogenesis, escape from immune surveillance, metastasis and drug resistance. In this study, we investigated whether T790M EGFR mutation-related gefitinib resistance could be transferred via TMV using lung cancer cells harboring exon 19 del mutation (PC-9 cells) ± exon 20 T790M mutation (PC-9/GR cells).

    Methods
    TMV were isolated from the culture medium by serial centrifugations. Isolated TMV were checked by electron microscopy for size and intact structure, and characteristic TMV markers (CD81 and ezrin) were verified by western blot analysis. Cytotoxic assay was done using XTT assay and EGFR mutation testing was done using PNA-clamping method.

    Results
    Incubation of PC-9 cells with TMV (40 μg/ml) derived from PC-9/GR cells confer PC-9 cells gefitinib-resistant. EGFR genotyping of TMV in both cells revealed as the same with cellular DNA and this means that TMV carry cell-specific DNA. Passage study after PC-9/GR cell derived TMV transfer showed, however, regained gefitinib sensitivity suggesting that TMV-mediated gefitinib resistance is phenotypically transient. Genotyping after T790M-containing TMV revealed EGFR WT.

    Conclusion
    T790M-associated gefitinib resistance in lung cancer cells might be horizontally transferred via TMV but this type transfer of gefitinib resistance was phenotypically transient in cell-line system and there was no genotype transfer. Further investigation for TMV-mediated transfer of gefitinib resistance is necessary.