Abstract
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.
Highlights
Urothelial bladder cancer (UBC) exhibits the highest mortality rate worldwide, being categorized as the second most common genitourinary disease in the USA [1]
Our results clearly indicate that T24 can serve as a powerful, informative, and versatile cell-line system that can be successfully exploited to illuminate the role of metabolic reprogramming in UBC progression toward metastasis
All cell lines were derived from urothelial cell carcinomas of human urinary bladder, with RT4 being classified as malignancy grade I, RT112 as grade I–II (II), T24 as grade III, and TCCSUP as grade IV
Summary
Urothelial bladder cancer (UBC) exhibits the highest mortality rate worldwide, being categorized as the second most common genitourinary disease in the USA [1]. UBC still remains a major clinical challenge and its treatment mainly depends on early diagnosis [2]. It can be generally classified as a low-grade (I and II) non-muscle-invasive and a high-grade (III and IV) muscle-invasive disease that is prone to metastasis, based on histological differentiations from normal bladder cells [3]. 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. 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
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