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Poster Session (ID 8)
- Event: ACLC 2018
- Type: Poster Session
- Presentations: 1
- Coordinates: 11/07/2018, 00:00 - 00:00, Poster Hall
P100 - Stem Cell Factor Leads to Lung Cancer Escapes from Anti-Angiogenic Therapy by Increasing the ALDH1+ Lung Cancer Cell Number (ID 146)
00:00 - 00:00 | Author(s): L. Wang
Although the anti-angiogenic therapy becomes an important treatment for non-small-cell lung cancer, cancer cells can escape from this therapy through several different ways so as to keep growth. Our previous results showed that anti-angiogenic drugs increased the number of ALDH1+ lung cancer cells in mouse models. This study is to explore the significance and mechanism of this phenomenon.
The xenograft tumor murine models and molecular experiments in vitro were used in this study.
In our experiments with murine lung cancer xenografts, we found that the anti-angiogenic agent endostatin increased the number of ALDH1+ lung caner cells. In vitro results showed that SOX and OCT4 were highly expressed in ALDH1+ lung cancer cells. These cells had stronger ability in surviving in hypoxic environment, metastasis and invasion than ALDH1- lung cancer cells. We also found that the expressions of HIF-1a and stem cell factor (SCF) in the xenografts were increased after anti-angiogenic therapy. HIF-1? could up-regulate the expression of SCF in lung cancer cells. The over-expression of SCF can increase the proportion of ALDH1+ cells in lung cancer. The mechanism was related to the HIF-1?/SCF/c-Kit/PI3K/AKT pathway. Finally, when we combined anti-angiogenic therapy with decreasing SCF expression, it is found that the survival time of mice in the combination group was significantly longer than that in the single anti-angiogenic group.
Anti-angiogenic therapy aggravated hypoxia which could induce the up-regulated expression of SCF in lung cancer. SCF promoted lung cancer to escape from anti-angiogenic therapy by increasing the number of ALDH1+ lung cancer cells.