Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Hatab, I.
The impact of ATGL on metabolism and angiogenesis in A549 lung carcinoma cell line under hypoxia.
Humanmedizin; [ Diplomarbeit ] Graz Medical University; 2020. pp. 98
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- Autor*innen der Med Uni Graz:
- Hatab Isra
- Betreuer*innen:
- Ghaffari Tabrizi-Wizsy Nassim
- Tomin Tamara
- Altmetrics:
- Abstract:
- Introduction Tumor cells perform angiogenesis and metabolic adjustments in response to their rapid growth and hypoxic microenvironment. Reduced levels of adipose triglyceride lipase (ATGL) - an enzyme involved in lipolysis - was reported in lung cancer cells and is associated with tumorigenesis, invasion and metastasis. Beside upregulation of angiogenesis and glycolysis, hypoxia lowers the expression of ATGL through activation of hypoxia inducible factor-1 (HIF-1). The aim of this study was to investigate the effect of hypoxia on the metabolism and angiogenic properties in ATGL deficient A549 cell line. Material and Methods The lung adenocarcinoma cell line A549 wild type (WT) and ATGL knockout (KO) were cultivated in 3-dimensional cell culture under 21% or 1% oxygen. Label free quantitative (LFQ) proteomic analysis was performed on the collected spheroids of WT and ATGL-KO. Supernatants of the spheroids were used in the chorioallantoic membrane (CAM) angiogenesis assay and newly formed blood vessels were counted. Results Our results from the proteomic analysis revealed an enhancement of glycolysis in the ATGL-KO than in WT cells under normoxia, following an increase in the anabolic reactions of lipid and protein. Furthermore, an increase of protein metabolism was seen in the normoxic compared to hypoxic WT spheroids. In addition, minor difference in the proteome composition was observed between WT and ATGL-KO under hypoxia and between normoxic and hypoxic ATGL-KO group. In the CAM assay, we observed significant angiogenic changes only in the A549-WT group versus ATGL-KO under 21% O2 (0.38 ± 0.03 vs 0.29 ± 0.03) (p = 0.018). Discussion Our results corresponded to previous studies, that loss of ATGL promotes Warburg effect, as well as induces proliferation of tumor cells. On the contrary, ATGL showed to be a proangiogenic factor in the in vivo assay, yet their signaling pathway is unclear. Further on, ATGL deficient and hypoxic A549 cells manifest similar phenotype. In conclusion, ATGL plays a significant role in the metabolism of NSCLC and can be used as potential prognostic and therapeutic factor. The function of ATGL deficiency could be mediated via the HIF-1 signaling pathway.