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Open AccessArticle

Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers

1
Section of Pharmaceutical Chemistry, Department of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens (NKUA), 15701 Athens, Greece
2
Section of Cell Biology and Biophysics, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 15701 Athens, Greece
3
Section of Animal and Human Physiology, Department of Biology, School of Science, National and Kapodistrian University of Athens (NKUA), 15701 Athens, Greece
4
Laboratory of Molecular Carcinogenesis and Rare Disease Genetics, Institute of Biosciences and Applications, National Center for Scientific Research (NCSR) “Demokritos”, 15701 Athens, Greece
5
Harvard Medical School, Massachusetts General Hospital Cancer Center (MGHCC), Charlestown, MA 021004, USA
*
Authors to whom correspondence should be addressed.
These authors contributed equally to this work.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(5), 1892; https://doi.org/10.3390/ijms21051892
Received: 31 January 2020 / Revised: 7 March 2020 / Accepted: 8 March 2020 / Published: 10 March 2020
Background: Urothelial bladder cancer (UBC) is one of the cancers with the highest mortality rate and prevalence worldwide; however, the clinical management of the disease remains challenging. Metabolomics has emerged as a powerful tool with beneficial applications in cancer biology and thus can provide new insights on the underlying mechanisms of UBC progression and/or reveal novel diagnostic and therapeutic schemes. Methods: A collection of four human UBC cell lines that critically reflect the different malignancy grades of UBC was employed; RT4 (grade I), RT112 (grade II), T24 (grade III), and TCCSUP (grade IV). They were examined using Nuclear Magnetic Resonance, Mass Spectrometry, and advanced statistical approaches, with the goal of creating new metabolic profiles that are mechanistically associated with UBC progression toward metastasis. Results: Distinct metabolic profiles were observed for each cell line group, with T24 (grade III) cells exhibiting the most abundant metabolite contents. AMP and creatine phosphate were highly increased in the T24 cell line compared to the RT4 (grade I) cell line, indicating the major energetic transformation to which UBC cells are being subjected during metastasis. Thymosin β4 and β10 were also profiled with grade-specific patterns of expression, strongly suggesting the importance of actin-cytoskeleton dynamics for UBC advancement to metastatic and drug-tolerant forms. Conclusions: The present study unveils a novel and putatively druggable metabolic signature that holds strong promise for early diagnosis and the successful chemotherapy of UBC disease. View Full-Text
Keywords: biomarker; bladder; cancer; grade; metabolomics; MS; NMR biomarker; bladder; cancer; grade; metabolomics; MS; NMR
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MDPI and ACS Style

Iliou, A.; Panagiotakis, A.; Giannopoulou, A.F.; Benaki, D.; Kosmopoulou, M.; Velentzas, A.D.; Tsitsilonis, O.E.; Papassideri, I.S.; Voutsinas, G.E.; Konstantakou, E.G.; Gikas, E.; Mikros, E.; Stravopodis, D.J. Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers. Int. J. Mol. Sci. 2020, 21, 1892. https://doi.org/10.3390/ijms21051892

AMA Style

Iliou A, Panagiotakis A, Giannopoulou AF, Benaki D, Kosmopoulou M, Velentzas AD, Tsitsilonis OE, Papassideri IS, Voutsinas GE, Konstantakou EG, Gikas E, Mikros E, Stravopodis DJ. Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers. International Journal of Molecular Sciences. 2020; 21(5):1892. https://doi.org/10.3390/ijms21051892

Chicago/Turabian Style

Iliou, Aikaterini; Panagiotakis, Aristeidis; Giannopoulou, Aikaterini F.; Benaki, Dimitra; Kosmopoulou, Mariangela; Velentzas, Athanassios D.; Tsitsilonis, Ourania E.; Papassideri, Issidora S.; Voutsinas, Gerassimos E.; Konstantakou, Eumorphia G.; Gikas, Evagelos; Mikros, Emmanuel; Stravopodis, Dimitrios J. 2020. "Malignancy Grade-Dependent Mapping of Metabolic Landscapes in Human Urothelial Bladder Cancer: Identification of Novel, Diagnostic, and Druggable Biomarkers" Int. J. Mol. Sci. 21, no. 5: 1892. https://doi.org/10.3390/ijms21051892

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