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Property "Has-20abstract" (as page type) with input value "-5B-5BFile:Foto-20Nivea-20Amoedo.jpg-7Cright-7C150px-7CNivea-20Amoedo-5D-5D-0AThe-20classic-20bioenergetic-20phenotype-20of-20cancer-20cells,-20an-20enhanced-20glycolysis-20with-20concomitant-20production-20of-20lactate-20even-20in-20high-20oxygen-20tension,-20was-20described-20by-20Otto-20Warburg-20approximately-2090-20years-20ago.-20However,-20the-20Warburg-20hypothesis-20does-20not-20necessarily-20imply-20mitochondrial-20dysfunction.-20Current-20thinking-20considers-20tumor-20cells-20as-20adapted-20to-20an-20oxygen-20gradient-20within-20the-20tumor-20mass.-20Those-20cells-20exposed-20to-20oxygen-20will-20utilize-20the-20gas-20and-20those-20found-20in-20hypoxic-20regions-20of-20the-20tumor-20will-20adjust-20by-20means-20of-20metabolic-20symbiosis.-20Tumor-20cells-20exhibit-20accelerated-20growth-20as-20well-20as-20metastasis,-20two-20major-20events-20that-20must-20be-20supported-20by-20sufficient-20energy-20supply.-20This-20can-20be-20translated-20as-20metabolic-20reprogramming-20that-20up-2Dregulates-20pathways-20that-20ultimately-20increase-20the-20rate-20of-20ATP-20production,-20synthesis-20of-20lipids-20and-20redox-20balance.-20According-20to-20Smolkovรก-20et-20al.-20-5B3-5D-20the-20process-20of-20carcinogenesis-20is-20guided-20by-20waves-20of-20gene-20expression-20that-20promote-20these-20metabolic-20changes.-20The-20energy-20metabolism-20of-20cancer-20cells-20is-20very-20heterogeneous.-20-20Indeed-20not-20all-20tumor-20cells-20display-20a-20high-20glycolytic-20flux-20as-20proposed-20by-20Warburg.-20Similarly,-20not-20all-20cancer-20cells-20grow-20fast-20and-20show-20intense-20anabolism.-20Furthermore,-20progression-20to-20metastasis-20appears-20to-20require-20mitochondrial-20function,-20a-20hypothesis-20that-20is-20compatible-20with-20the-20results-20obtained-20by-20our-20group.-20In-20order-20to-20show-20this,-20we-20resorted-20to-20a-20murine-20model-20of-20melanoma.-20In-20this-20model-20a-20melanocyte-20cell-20line-20was-20subjected-20to-20several-20cycles-20of-20adhesion-20impediment,-20which-20produced-20stable-20cell-20lines-20exhibiting-20phenotypes-20corresponding-20to-20a-20progression-20from-20non-2Dtumorigenic-20to-20metastatic-20cells.-20The-20different-20stages-20of-20malignant-20transformation-20were-20as-20follows:-20Non-2Dtumorigenic-20cells-20melan-2Da-20(-27-27'ma-27-27')-20(original-20murine-20melanocytes)-3B-20non-2Dtumorigenic-20cell-20line-20-27-27'4C-27-27'-20(obtained-20after-204-20cycles-20of-20adherence-20abrogation)-3B-20non-2Dmetastatic-20-27-27'4C11-2D-27-27'-20and-20metastatic-20-27-27'4C11+-27-27'-20melanoma-20cell-20lines,-20which-20were-20obtained-20by-20diluting-20the-20cells-20from-20the-20spheroids-20of-20the-20-27-27'4C-27-27'-20cell-20line.-20The-20metabolic-20profile-20of-20each-20of-20these-20different-20cell-20lines-20was-20investigated-20by-20evaluating-20enzyme-20activities-20and-20expression-20of-20members-20of-20the-20glycolytic-20and-20oxidative-20pathways.-20Our-20results-20showed-20that-20metastatic-20cell-20line-20(-27-27'4C11+-27-27')-20released-20the-20highest-20amounts-20of-20lactate-20and-20exhibited-20high-20LDH-20activity,-20typical-20of-20the-20Warburg-20effect.-20In-20contrast,-20results-20obtained-20with-20-5B-5Bhigh-2Dresolution-20respirometry-5D-5D-20with-20-27-27'4C11+-27-27'-20intact-20cells-20showed-20an-20increased-20oxidative-20metabolism,-20with-20enhanced-20rates-20of-20oxygen-20consumption-20coupled-20to-20ATP-20synthesis-20when-20compared-20to-20the-20other-20pre-2Dmalignant-20stages.-20Moreover-20we-20observed-20an-20increase-20in-20succinate-20dehydrogenase-20(Complex-20II)-20activity-20in-20these-20cells.-20Concomitantly,-20we-20detected-20an-20increase-20in-20activity-20of-20the-20electron-20transport-20system-20(-5B-5BET-2Dpathway-5D-5D-20capacity).-20We-20did-20not-20observe-20an-20increase-20in-20mitochondrial-20content,-20mitochondrial-20biogenesis,-20nor-20alterations-20in-20fusion-20and-20fission-20process.-20These-20results-20suggest-20enhanced-20-5B-5BOXPHOS-5D-5D.-20This-20was-20thought-20to-20be-20associated-20to-20metastasis,-20a-20condition-20which-20would-20benefit-20from-20unrestricted-20supply-20of-20oxygen.-20Detailed-20analysis-20of-20patterns-20in-20this-20and-20other-20models-20of-20tumor-20progression-20may-20reveal-20whether-20the-20modulation-20of-20the-20oxidative-20metabolism-20is-20a-20feature-20of-20the-20metastatic-20process.-0A-23-20-5Bhttp:-2F-2Fwww.ncbi.nlm.nih.gov-2Fpubmed-3Fterm=Melanocyte-2520transformation-2520associated-2520with-2520substrate-2520adhesion-2520impediment-20Oba-2DShinjo-20SM,-20Correa-20M,-20Ricca-20TI,-20Molognoni-20F,-20Pinhal-20MA,-20Neves-20IA,-20Marie-20SK,-20Sampaio-20LO,-20Nader-20HB,-20Chammas-20R,-20Jasiulionis-20MG-20(2006)-20Melanocyte-20transformation-20associated-20with-20substrate-20adhesion-20impediment.-20Neoplasia-208:-20231-2D241.-20Open-20Access-5D-0A-23-20-5Bhttp:-2F-2Fwww.ncbi.nlm.nih.gov-2Fpubmed-2F22664330-20Vaupel-20P,-20Mayer-20A-20(2012)-20Availabilit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