title: Unique fractal evaluation and therapeutic implications of mitochondrial morphology in malignant mesothelioma.
abstract: Malignant mesothelioma (MM), is an intractable disease with limited therapeutic options and grim survival rates. Altered metabolic and mitochondrial functions are hallmarks of MM and most other cancers. Mitochondria exist as a dynamic network, playing a central role in cellular metabolism. MM cell lines display a spectrum of altered mitochondrial morphologies and function compared to control mesothelial cells. Fractal dimension and lacunarity measurements are a sensitive and objective method to quantify mitochondrial morphology and most importantly are a promising predictor of response to mitochondrial inhibition. Control cells have high fractal dimension and low lacunarity and are relatively insensitive to mitochondrial inhibition. MM cells exhibit a spectrum of sensitivities to mitochondrial inhibitors. Low mitochondrial fractal dimension and high lacunarity correlates with increased sensitivity to the mitochondrial inhibitor metformin. Lacunarity also correlates with sensitivity to Mdivi-1, a mitochondrial fission inhibitor. MM and control cells have similar sensitivities to cisplatin, a chemotherapeutic agent used in the treatment of MM. Neither oxidative phosphorylation nor glycolytic activity, correlated with sensitivity to either metformin or mdivi-1. Our results suggest that mitochondrial inhibition may be an effective and selective therapeutic strategy in mesothelioma, and identifies mitochondrial morphology as a possible predictor of response to targeted mitochondrial inhibition.
authors.affiliation: Department of Medicine, Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Frances E
authors.initials: FE
authors.lastname: Lennon
authors.affiliation: Department of Cell and Molecular Biology, Feinberg School of Medicine, Northwestern University, Chicago, IL, 60611, USA.
authors.forename: Gianguido C
authors.initials: GC
authors.lastname: Cianci
authors.affiliation: Department of Medicine, Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Rajani
authors.initials: R
authors.lastname: Kanteti
authors.affiliation: Department of Medicine, Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Jacob J
authors.initials: JJ
authors.lastname: Riehm
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Qudsia
authors.initials: Q
authors.lastname: Arif
authors.affiliation: Department of Medical Oncology and Therapeutics Research, City of Hope, Duarte, CA 91010, USA.
authors.forename: Valeriy A
authors.initials: VA
authors.lastname: Poroyko
authors.affiliation: University of Maryland, College Park, MD, 20742, USA.
authors.forename: Eitan
authors.initials: E
authors.lastname: Lupovitch
authors.affiliation: Department of Surgery, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Wickii
authors.initials: W
authors.lastname: Vigneswaran
authors.affiliation: Department of Pathology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Aliya
authors.initials: A
authors.lastname: Husain
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Phetcharat
authors.initials: P
authors.lastname: Chen
authors.affiliation: Department of Medicine, Section of Cardiology, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: James K
authors.initials: JK
authors.lastname: Liao
authors.affiliation: Department of Medicine, Hematology/Oncology, Dana-Farber Cancer Institute, Boston, MA, 02215, USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Sattler
authors.affiliation: Department of Medicine, Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Hedy L
authors.initials: HL
authors.lastname: Kindler
authors.affiliation: Department of Medicine, Section of Hematology/Oncology and the Comprehensive Cancer Center, University of Chicago, Chicago, IL, 60637, USA.
authors.forename: Ravi
authors.initials: R
authors.lastname: Salgia
mesh_terms: D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D017709:Fractals; D006019:Glycolysis; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology*; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology*; D000086002:Mesothelioma, Malignant; D008687:Metformin / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D024101:Mitochondrial Proteins / Q000378:metabolism
chemical_list: D024101:Mitochondrial Proteins; D008687:Metformin; D002945:Cisplatin