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Rui Zhang

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    P1.02 - Biology/Pathology (ID 614)

    • Event: WCLC 2017
    • Type: Poster Session with Presenters Present
    • Track: Biology/Pathology
    • Presentations: 1
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      P1.02-067 - FGF1 and IGF1 Co-Stimulation Promoted the Amplification and Cancer Stemness of Lung Cancer Cells under 3D Culture Condition (ID 8589)

      09:30 - 16:00  |  Presenting Author(s): Rui Zhang

      • Abstract
      • Slides

      Lung cancer stem cells (LCSCs) are considered as the cellular origins of metastasis and relapse of lung cancer. However, because of relative few amount of stationary LCSCs in primary cancer tissues, it is difficult to conduct large-scale mechanical and translational studies directly without any amplification of LCSCs in vitro. Routine two-dimentional culture system(2D-culture) hardly mimics the growth and functions of LCSCs in vivo and therefore significantly decreases the stemness activity of LCSCs.

      We cultured human lung adenocarcinoma cell line A549 in basal medium eagle (BME) to establish three-dimentional (3D) culture condition, followed by screening cytokines that promote cancer stem cells’ growth under 3D condition culture. To investigate their functions in enrichment of lung cancer stem-like cells, we constructed a conditioned 3D culture model and performed a serious of assays. We detected expression of stemness markers by flow cytometry and RT-qPCR, and stem cell like phenotypes including cell proliferation, colony formation, mammosphere culture, cell apoptosis, migration, invasion and drug resistance in vitro, as well as tumorigenicity in vivo. Furthermore, we explored the signaling pathways involved in regulating enrichment and amplification of lung cancer stem-like cells by Affymetrix HTA 2.0 Array.

      We found 3D-culture promoted the enrichment and amplification of LCSCs in A549 cells which displaying higher proliferation and invasion activity, but lower apoptosis. The expression and secretion levels of FGF1 and IGF1 were dramatically elevated in 3D-culture compared to 2D-culture. After growing in FGF1 and IGF1-conditioned 3D-culture, the proportion of LCSCs with specific stemness phenotypes in A549 cells significantly increased compared to that in either traditional 2D or conventional 3D system. FGF1 and IGF1 promoted proliferation and invasion activity, as well as elevated drug resistance of LCSCs. Further results indicated that FGF1 and IGF1 promoted the amplification and cancer stemness of LCSCs dependent on MAPK signaling pathway.

      Our data firstly established a cytokines-conditioned 3D-culture for LCSCs and demonstrated the effects of FGF1 and IGF1 in promoting the enrichment and amplification of LCSCs which might provide a feasible cell models in vitro for both mechanical and translational researches on lung cancer.

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