title: Potential Indexing of the Invasiveness of Breast Cancer Cells by Mitochondrial Redox Ratios.
abstract: The invasive/metastatic potential of cancer cells is an important factor in tumor progression. The redox ratios obtained from ratios of the endogenous fluorescent signals of NADH and FAD, can effectively respond to the alteration of cancer cells in its mitochondrial energy metabolism. It has been shown previously that the redox ratios may predict the metastatic potential of cancer mouse xenografts. In this report, we aimed to investigate the metabolic state represented by the redox ratios of cancer cells in vitro. Fluorescence microscopic imaging technology was used to observe the changes of the endogenous fluorescence signals of NADH and FAD in the energy metabolism pathways. We measured the redox ratios (FAD/NADH) of breast cancer cell lines MDA-MB-231, MDA-MB-468, MCF-7, and SKBR3. We found that the more invasive cancer cells have higher FAD/NADH ratios, largely consistent with previous studies on breast cancer xenografts. Furthermore, by comparing the fluorescence signals of the breast cancer cells under different nutritional environments including starvation and addition of glutamine, pyruvate and lactate, we found that the redox ratios still effectively distinguished the highly invasive MDA-MB-231 cells from less invasive MCF-7 cells. These preliminary data suggest that the redox ratio may potentially provide a new index to stratefy breast cancer with different degrees of aggressiveness, which could have significance for the diagnosis and treatment of breast cancer.
authors.affiliation: Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Department of Biomedical Engineering, MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, China.|Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Wuhan, Hubei, China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Radiology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.|Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: He N
authors.initials: HN
authors.lastname: Xu
authors.affiliation: Britton Chance Center for Biomedical Photonics, Wuhan National Laboratory for Optoelectronics, Huazhong University of Science and Technology, Wuhan, Hubei, China.
authors.forename: Qingming
authors.initials: Q
authors.lastname: Luo
authors.affiliation: Molecular Imaging Laboratory, Department of Radiology, Britton Chance Laboratory of Redox Imaging, Johnson Research Foundation, Department of Biochemistry and Biophysics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. linli@mail.med.upenn.edu.
authors.forename: Lin Z
authors.initials: LZ
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D002465:Cell Movement; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005182:Flavin-Adenine Dinucleotide / Q000378:metabolism; D006801:Humans; D061986:MCF-7 Cells; D008856:Microscopy, Fluorescence; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D009243:NAD / Q000378:metabolism; D009361:Neoplasm Invasiveness; D010084:Oxidation-Reduction; D012402:Rotenone / Q000494:pharmacology; D059016:Tumor Microenvironment; D014475:Uncoupling Agents / Q000494:pharmacology
chemical_list: D014408:Biomarkers, Tumor; D014475:Uncoupling Agents; D012402:Rotenone; D009243:NAD; D005182:Flavin-Adenine Dinucleotide
keywords: Breast cancer; FAD; Invasive potential; NADH; Redox ratio