Author of

• 11503

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  P2.03 - Poster Session 2 - Technology and Novel Development (ID 151)

  • Event: WCLC 2013
  • Type: Poster Session
  • Track: Biology
  • Presentations: 1
  • Moderators:
  • Coordinates: 10/29/2013, 09:30 - 16:30, Exhibit Hall, Ground Level

  • 11505

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    P2.03-002 - Circulating Tumor Cells from 4D Model Mimic Metastatic Pattern in vivo and Gene Expression Profile Predicts Poor Prognosis in Lung Cancer Patients (ID 228)

    09:30 - 09:30  |  Author(s): M.J. Thrall
    • Abstract

    Background
    Circulating tumor cells are tumor cells found in the vasculature or lymphatics of cancer patients that are thought to be responsible for metastasis. Recently, we developed an ex vivo 4D lung cancer model that forms perfusable tumor nodules. We have found that there are live tumor cells in the circulation in the model (CTCs). In this study, we aim to determine (i) the characteristics of these cells in vivo and (ii) whether the gene expression profile signature of these cells predicts survival in patients with lung cancer.

    Methods
    We used 393P and 344SQ mouse lung cancer cells for the in vivo experiment. The 393P cells that were grown on petri dish (2D) did not form metastatic lesions when injected into the flank of 129sv mice while 344SQ 2D cells did form metastatic lesions. Both cells were grown in the 4D model. We measured the size of the tumors and the number of CTCs for 14 days. We analyzed the mesenchymal characterisitics of 2D vs CTCs. We injected the CTCs in the tail vein of the 129sv mice and determined if they formed metastasis. We used A549 cells for the gene expression experiment. We placed the A549 2D cells in the 4D model and measured the size of the tumors and the number of CTCs. We compared the gene expression profile (Human OneArray v5 chip) of A549 2D against the A549 CTCs. We analyzed the differential gene signature in human lung cancer database for survival.

    Results
    All of the cell lines formed perfusable lung nodules in the 4D model by day 2 and formed circulating tumor cells starting day 5. The 344SQ cells grew faster (p = 0.01) and formed more circulating tumor cells (p = 0.8) compared to the 393P cells initially but by day 14 there was no significant difference in tumor size (p = 0.8) and number of circulating tumor cells (p = 0.7). The 393P CTCs were less mesenchymal (lower CDH2 (p < 0.0001), ZEB1 (p = 0.001) and VIM (p < 0.0001)) compared to 393P 2D while 344SQ CTCs were more mesenchymal (higher CDH2 (p < 0.0001), ZEB1 (p < 0.0001) and VIM (p < 0.0001)) compared to 344SQ 2D. When 393P CTCs were injected into the tail vein of 129sv mice, they did not form metastatic lesions while 344SQ CTCs formed metastatic lesions in the lung. Gene expression analysis of A549 2D compared to A549 CTCs showed that there were 2504 gene probes that were differentially expressed. This signature correlated with poor survival in patients with lung cancer (n = 1492, Log rank p = 2.6 x 10[-5]).

    Conclusion
    The circulating tumor cells that were isolated from the ex vivo 4D lung cancer model mimic the pattern of metastasis in vivo. Moreover, the circulating tumor cell signature correlates with poor survival in patients with lung cancer. The circulating tumor cells that are isolated in the ex vivo 4D lung cancer model may be the cells responsible for metastasis.