Abstract
Mitochondrial bioenergetics reprogramming is an essential response of cells to stress. Platelets, an accessible source of mitochondria, have a crucial role in cancer development; however, the platelet mitochondrial function has not been studied in urothelial carcinoma (UC) patients. A total of 15 patients with UC and 15 healthy controls were included in the study. Parameters of platelet mitochondrial respiration were evaluated using the high-resolution respirometry method, and the selected antioxidant levels were determined by HPLC. In addition, oxidative stress was evaluated by the thiobarbituric acid reactive substances (TBARS) concentration in plasma. We demonstrated deficient platelet mitochondrial respiratory chain functions, oxidative phosphorylation (OXPHOS), and electron transfer (ET) capacity with complex I (CI)-linked substrates, and reduced the endogenous platelet coenzyme Q10 (CoQ10) concentration in UC patients. The activity of citrate synthase was decreased in UC patients vs. controls (p = 0.0191). γ-tocopherol, α-tocopherol in platelets, and β-carotene in plasma were significantly lower in UC patients (p = 0.0019; p = 0.02; p = 0.0387, respectively), whereas the plasma concentration of TBARS was increased (p = 0.0022) vs. controls. The changes in platelet mitochondrial bioenergetics are consistent with cell metabolism reprogramming in UC patients. We suppose that increased oxidative stress, decreased OXPHOS, and a reduced platelet endogenous CoQ10 level can contribute to the reprogramming of platelet mitochondrial OXPHOS toward the activation of glycolysis. The impaired mitochondrial function can contribute to increased oxidative stress by triggering the reverse electron transport from the CoQ10 cycle (Q-junction) to CI.
Highlights
Bladder cancer is the tenth most common form of cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths in 2018 [1]
Blood Counts and Selected Metabolic Parameters of Subjects in Both Groups In urothelial carcinoma (UC) patients, both the red blood cell count and hemoglobin were significantly decreased vs. the control group (p < 0.0062 and p = 0.0014, respectively), whereas creatinine, urea, and uric acid were higher in UC patients in comparison to the control subjects (p < 0.0002, p = 0.0003 and p < 0.0107, respectively)
Platelet mitochondrial bioenergetics have been studied in various diseases [10,11,12,13,14,15,16], and in thrombocytopenic patients undergoing chemotherapy [21]
Summary
Bladder cancer is the tenth most common form of cancer worldwide, with an estimated 549,000 new cases and 200,000 deaths in 2018 [1]. Malignant bladder tumors are approximately four times more common in men than in women, with incidence and mortality rates of 9.6 and 3.2 per 100,000 people, respectively. 15% of bladder cancer patients have distant metastases at the initial diagnosis [2]. In approximately 25% of cases, UC differentiates into various histological subtypes; the prognosis of some variants, e.g., plasmacytoid and sarcomatoid, are worse [4]. The platelets and their role in cancer development have been in the spotlight for many years, with the first mentions dating back to the early 1970s [5,6,7]. In line with current knowledge, platelets in the blood circulation activate and encase the malignant cells detached from the primary tumor due to the secretion of growth factors and chemokines, such as vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), or transforming growth factor β (TGF-β)
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