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Property "Has-20abstract" (as page type) with input value "The-20classic-20bioenergetic-20phenotype-20of-20cancer-20cells-20of-20enhanced-20glycolysis-20was-20described-20by-20Otto-20Warburg-20approximately-2090-20years-20ago.-20However,-20the-20Warburg-20hypothesis-20does-20not-20necessarily-20imply-20mitochondrial-20dysfunction.-20Current-20thinking-20envisages-20tumor-20cells-20as-20compliant-20to-20an-20oxygen-20gradient-20within-20the-20tumor-20mass.-20Those-20cells-20on-20the-20periphery-20utilize-20oxygen-20whereas-20those-20found-20in-20hypoxic-20regions-20display-20metabolic-20symbiosis-20with-20the-20adjacent-20stromal-20cells-20-5B1-5D.-20Essentially-20metabolic-20reprograming-20means-20up-2Dregulation-20of-20pathways-20that-20increase-20the-20rate-20of-20ATP-20production,-20synthesis-20of-20lipids-20and-20redox-20balance.-20The-20process-20of-20carcinogenesis-20is-20guided-20by-20gene-20expression-20regulation-20that-20promote-20these-20metabolic-20changes-20in-20a-20different-20and-20complex-20way-20for-20each-20cancer-20cell,-20thus,-20the-20energy-20metabolism-20of-20cancer-20cells-20is-20very-20heterogeneous.-20For-20example,-20not-20all-20tumor-20cells-20display-20a-20high-20glycolytic-20flux-20as-20proposed-20by-20Warburg.-20Progression-20to-20metastasis-20appears-20to-20require-20mitochondrial-20function,-20a-20hypothesis-20that-20is-20compatible-20with-20the-20results-20obtained-20by-20our-20group.-20-0A-0AIn-20order-20to-20show-20this-20we-20resorted-20an-20experimental-20model-20of-20murine-20melanoma-20cells.-20A-20melanocyte-20cell-20line-20was-20subjected-20to-20several-20cycles-20of-20adhesion-20impediment,-20producing-20stable-20cell-20lines-20exhibiting-20phenotypes-20representing-20a-20progression-20from-20non-2Dtumorigenic-20to-20metastatic-20cells.-20These-20were:-20non-2Dtumorigenic-20cells-20melan-2Da-20(ma)-3B-20non-2Dtumorigenic-20cell-20line-204C-20(obtained-20after-204-20cycles-20of-20adherence-20abrogation)-3B-20non-2Dmetastatic-204C11-2D-20and-20metastatic-204C11+-20melanoma-20cell-20lines.-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-20-5B2-5D.-20-0A-0AOur-20results-20showed-20that-20only-20metastatic-20cell-20line-20(4C11+)-20released-20the-20highest-20amounts-20of-20lactate-20and-20exhibited-20high-20LDH-20activity-20related-20to-20glutamine-20catabolism.-20In-20contrast,-20high-2Dresolution-20respirometry-20(HRR)-20showed-20that-204C11+-20intact-20cells-20had-20increased-20(2.8-2Dfold)-20oxidative-20metabolism,-20with-20enhanced-20(2.6-2Dfold)-20oxygen-20flux-20coupled-20to-20ATP-20synthesis-20when-20compared-20to-20the-20other-20pre-2Dmalignant-20stages.-20Moreover,-20in-204C11+-20cells,-20we-20observed-20an-20increase-20in-20succinate-20dehydrogenase-20(Complex-20II)-20activity-20confirmed-20by-20HRR-20in-20permeabilized-20cells.-20We-20did-20not-20observe-20an-20increase-20in-20mitochondrial-20content,-20mitochondrial-20biogenesis,-20but-20we-20observed-20an-20increase-20(2-2Dfold)-20in-20fission-20process.-20These-20results-20suggest-20enhanced-20OXPHOS.-20This-20was-20thought-20to-20be-20associated-20to-20metastasis,-20a-20condition-20which-20would-20benefit-20from-20unrestricted-20supply-20of-20oxygen.-20-0A-0ADetailed-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.-20To-20test-20this-20hypothesis-20we-20produced-204C11+-20Rho-200-20cells.-20Preliminary-20results-20showed-20a-20decreased-20in-20proliferation." contains invalid characters or is incomplete and therefore can cause unexpected results during a query or annotation process.

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