Yu Wen1,2, He N Xu2, Lisa Privette Vinnedge3,4, Min Feng2, Lin Z Li5,6. 1. Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, 08903, USA. 2. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. 3. Cincinnati Children's Hospital Medical Center, Cancer and Blood Diseases Institute, Cincinnati, OH, USA. 4. Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA. 5. Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. linli@pennmedicine.upenn.edu. 6. Abramson Cancer Center and Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. linli@pennmedicine.upenn.edu.
Abstract
PURPOSE: Optical redox imaging (ORI), based on collecting the endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) containing a redox cofactor flavin adenine dinucleotide (FAD), provides sensitive indicators of cellular metabolism and redox status. ORI indices (such as NADH, FAD, and their ratio) have been under investigation as potential progression/prognosis biomarkers for cancer. Higher FAD redox ratio (i.e., FAD/(FAD + NADH)) has been associated with higher invasive/metastatic potential in tumor xenografts and cultured cells. This study is to examine whether ORI indices can respond to the modulation of oncogene DEK activities that change cancer cell invasive/metastatic potential. PROCEDURES: Using lentiviral shRNA, DEK gene expression was efficiently knocked down in MDA-MB-231 breast cancer cells (DEKsh). These DEKsh cells, along with scrambled shRNA-transduced control cells (NTsh), were imaged with a fluorescence microscope. In vitro invasive potential of the DEKsh cells and NTsh cells was also measured in parallel using the transwell assay. RESULTS: FAD and FAD redox ratios in polyclonal cells with DEKsh were significantly lower than that in NTsh control cells. Consistently, the DEKsh cells demonstrated decreased invasive potential than their non-knockdown counterparts NTsh cells. CONCLUSIONS: This study provides direct evidence that oncogene activities could mediate ORI-detected cellular redox state.
PURPOSE: Optical redox imaging (ORI), based on collecting the endogenous fluorescence of reduced nicotinamide adenine dinucleotide (NADH) and oxidized flavoproteins (Fp) containing a redox cofactor flavin adenine dinucleotide (FAD), provides sensitive indicators of cellular metabolism and redox status. ORI indices (such as NADH, FAD, and their ratio) have been under investigation as potential progression/prognosis biomarkers for cancer. Higher FAD redox ratio (i.e., FAD/(FAD + NADH)) has been associated with higher invasive/metastatic potential in tumor xenografts and cultured cells. This study is to examine whether ORI indices can respond to the modulation of oncogene DEK activities that change cancer cell invasive/metastatic potential. PROCEDURES: Using lentiviral shRNA, DEK gene expression was efficiently knocked down in MDA-MB-231breast cancer cells (DEKsh). These DEKsh cells, along with scrambled shRNA-transduced control cells (NTsh), were imaged with a fluorescence microscope. In vitro invasive potential of the DEKsh cells and NTsh cells was also measured in parallel using the transwell assay. RESULTS:FAD and FAD redox ratios in polyclonal cells with DEKsh were significantly lower than that in NTsh control cells. Consistently, the DEKsh cells demonstrated decreased invasive potential than their non-knockdown counterparts NTsh cells. CONCLUSIONS: This study provides direct evidence that oncogene activities could mediate ORI-detected cellular redox state.
Entities:
Keywords:
Breast cancer; DEK gene; FAD; Invasive potential; Knock down; NADH; Optical redox imaging; Redox ratio
Authors: Aziz Ul Rehman; Ayad G Anwer; Martin E Gosnell; Saabah B Mahbub; Guozhen Liu; Ewa M Goldys Journal: Biomed Opt Express Date: 2017-02-10 Impact factor: 3.732
Authors: Trisha M Wise-Draper; Hillary V Allen; Megan N Thobe; Elizabeth E Jones; Kristen B Habash; Karl Münger; Susanne I Wells Journal: J Virol Date: 2005-11 Impact factor: 5.103
Authors: Julie Hanson Ostrander; Christine M McMahon; Siya Lem; Stacy R Millon; J Quincy Brown; Victoria L Seewaldt; Nimmi Ramanujam Journal: Cancer Res Date: 2010-05-11 Impact factor: 12.701