Karavyraki 2017 Abstract IOC122

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Mitochondrial function and morphology linked to metabolic differences in normal, dysplastic and cancerous oral cells.

Link: Mitochondr Physiol Network 22.01

Karavyraki M, Porter RK (2017)

Event: IOC122

Oral squamous cell carcinoma (OSCC) is the sixth most common cancer in the world and accounts for more than 90% of oral malignancies. OSCC is usually preceded by the oral premalignant lesions, mainly oral leukoplakia (OLK) after repeated insults of carcinogens, tobacco. Dysplastic oral keratinocyte (DOK) cells were firstly isolated from a 57-year-old man who was a heavy smoker prior to the appearance of a white patch on his tongue. Eleven years later a squamous-cell carcinoma developed at the site and was excised. Subsequently the remaining dysplasia was removed, and it was from a piece of this that the primary cell cultures which eventually gave rise to DOK were initiated. The DOK line has been single-cell cloned and is apparently immortal (SCC) [1]. Mitochondria and mitochondrial proteins are undoubtedly potential anti-cancer targets. Mitochondria are the site of oxidative phosphorylation. Mitochondrial morphology is sensitive to stress and respond dynamically to the changes in their cellular microenvironment. Mitochondrial dysfunction is also a hallmark of many diseases. For instance complex I subunit mutations and citric acid cycle enzyme mutations are associated with several cancers [2,3].

The aim of this project is to characterize differential mitochondrial function/morphology in comparisons of normal, dysplastic and cancerous oral cells.

Our initial focus will be on a mitochondrial functional/morphological comparison of normal tongue cells, the dysplastic tongue cell line (DOK) and tongue carcinoma cell line (SCC-4). Cells will be characterised for invasiveness, migration, anoikis resistance and hypoxia while their bioenergetic profiling will be examined by Oroboros high-resolution respirometry and Seahorse Extracellular Flux Analysis. Further to their mitochondrial morphology and dynamics, Confocal Microscopy will be applied, while Quantitative RT-PCR & immunoblotting will be used to analyze their mitochondrial protein expression levels. Through Chemotherapy sensitivity will be analyzed their differential drug profiling of defined stages of OSCC correlated to mitochondrial function, while NMR metabolite analysis will be used to investigate their Metabolic Profiling.

The predicted outcome of this project will be the discovery of differential mitochondrial abundance, morphology, functional proteins involved in mitochondrial dynamics and metabolic differences in normal, dysplastic and oral cancer cells. These discoveries will lead to the identification of novel therapeutic targets.


Bioblast editor: Kandolf G O2k-Network Lab: IE Dublin Porter RK


Labels: MiParea: Respiration, Exercise physiology;nutrition;life style, mt-Medicine  Pathology: Cancer 

Organism: Human  Tissue;cell: Endothelial;epithelial;mesothelial cell 



HRR: Oxygraph-2k 


Affiliations

School Biochem Immunol, Trinity Biomed Sci Inst (TBSI), Trinity College Dublin, Ireland. – karavyrm@tcd.ie

Figure 1

Figure 1

References

  1. Dong Y, Zhao Q, Ma X, Ma G, Liu C, Chen Z, Yu L, Liu X, Zhang Y, Shao S, Xiao J, Li J, Zhang W, Fu M, Dong L, Yang X, Guo X, Xue L, Fang F, Zhan Q, Zhang L (2015) Establishment of a new OSCC: cell line derived from OKL and identification of malignant transformation-related proteins by differential proteomics approach. Sci Rep 5:12668.
  2. Wallace DC (2012) Mitochondria and Cancer. Nature Rev 12:685-98.
  3. Galluzzi L, Kepp O, Heiden MGV, Kroemer G (2013) Metabolic targets for cancer therapy. Nature Rev Drug Discov 12:829-46.