title: UVA-Irradiation Induces Melanoma Invasion via the Enhanced Warburg Effect.
abstract: Melanoma is a malignant tumor in which UVA (320-400 nm) radiation is considered to be an important risk factor. But the role of UVA in melanoma progression toward an invasive phenotype is still not adequately investigated. For most proliferating tumor cells the preference of aerobic glycolysis has been described as the Warburg effect. Here we investigate the effect of UVA irradiation on changes in the Warburg effect and tumor progression toward invasive potential. On UVA irradiation, melanoma cell lines from initial tumors show an induction of the Warburg effect with increased glucose consumption and lactate production, which is at least partially mediated by reactive oxygen species. Associated with UVA treatment and enhanced lactic acid production, tumor-relevant proteases and in situ invasion is upregulated. Simultaneously, UVA increases intracellular concentrations of progression marker transketolase and activated protein kinase Akt, both involved in metabolic changes that increase with proliferation. Using invasion assays we show that lactic acid, resulting from the UVA enhanced and partially reactive oxygen species-mediated Warburg effect, increases the invasive potential of all melanoma cell lines investigated. Therefore, we demonstrate in melanoma cells that production of lactic acid, induced by UVA irradiation, increases invasiveness of melanoma cells via expression of tumor-relevant proteases.
authors.affiliation: Department of Dermatology, University Hospital Regensburg, Regensburg, Germany; Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: York
authors.initials: Y
authors.lastname: Kamenisch
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Tarza S A
authors.initials: TSA
authors.lastname: Baban
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Winfried
authors.initials: W
authors.lastname: Schuller
authors.affiliation: Department of Neurology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Anna-Katharina
authors.initials: AK
authors.lastname: von Thaler
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Tobias
authors.initials: T
authors.lastname: Sinnberg
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Gisela
authors.initials: G
authors.lastname: Metzler
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Jürgen
authors.initials: J
authors.lastname: Bauer
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Birgit
authors.initials: B
authors.lastname: Schittek
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Claus
authors.initials: C
authors.lastname: Garbe
authors.affiliation: Department of Dermatology, Eberhard Karls University, Tübingen, Germany.
authors.forename: Martin
authors.initials: M
authors.lastname: Rocken
authors.affiliation: Department of Dermatology, University Hospital Regensburg, Regensburg, Germany. Electronic address: Mark.Berneburg@ukr.de.
authors.forename: Mark
authors.initials: M
authors.lastname: Berneburg
mesh_terms: D001786:Blood Glucose / Q000032:analysis; D045744:Cell Line, Tumor / Q000528:radiation effects; D005500:Follow-Up Studies; D006801:Humans; D019344:Lactic Acid / Q000378:metabolism; D008545:Melanoma / Q000209:etiology / Q000473:pathology*; D009361:Neoplasm Invasiveness / Q000473:pathology; D009381:Neoplasms, Radiation-Induced / Q000473:pathology; D011829:Radiation Dosage; D060888:Real-Time Polymerase Chain Reaction / Q000379:methods; D018570:Risk Assessment; D012878:Skin Neoplasms / Q000209:etiology / Q000473:pathology*; D014466:Ultraviolet Rays / Q000009:adverse effects*; D000096142:Cutaneous Malignant Melanoma
chemical_list: D001786:Blood Glucose; D019344:Lactic Acid