Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties
Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading an...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2020-12-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/9/12/2669 |
| _version_ | 1827700243790036992 |
|---|---|
| author | Valentina Pasquale Giacomo Ducci Gloria Campioni Adria Ventrici Chiara Assalini Stefano Busti Marco Vanoni Riccardo Vago Elena Sacco |
| author_facet | Valentina Pasquale Giacomo Ducci Gloria Campioni Adria Ventrici Chiara Assalini Stefano Busti Marco Vanoni Riccardo Vago Elena Sacco |
| author_sort | Valentina Pasquale |
| collection | DOAJ |
| description | Bladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration. In contrast, RT112 cells are more prone to form spheroids. RT112 cells produce more ATP by glycolysis and OXPHOS, present overall higher metabolic plasticity and are less sensitive than 5637 to nutritional perturbation of cell proliferation and migration induced by treatment with 2-deoxyglucose and metformin. On the contrary, spheroid formation is less sensitive to metabolic perturbations in 5637 than RT112 cells. The ability of metformin to reduce, although with different efficiency, cell proliferation, sphere formation and migration in both cell lines, suggests that OXPHOS targeting could be an effective strategy to reduce the invasiveness of Grade 2 bladder cancer cells. |
| first_indexed | 2024-03-10T14:07:34Z |
| format | Article |
| id | doaj.art-290453ca75714338b4f750d75966464b |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-10T14:07:34Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-290453ca75714338b4f750d75966464b2023-11-21T00:27:08ZengMDPI AGCells2073-44092020-12-01912266910.3390/cells9122669Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness PropertiesValentina Pasquale0Giacomo Ducci1Gloria Campioni2Adria Ventrici3Chiara Assalini4Stefano Busti5Marco Vanoni6Riccardo Vago7Elena Sacco8Department of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyUrological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Hospital, 20132 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyUrological Research Institute, Division of Experimental Oncology, IRCCS San Raffaele Hospital, 20132 Milan, ItalyDepartment of Biotechnology and Biosciences, University of Milano-Bicocca, Piazza della Scienza 2, 20126 Milan, ItalyBladder cancer is one of the most prevalent deadly diseases worldwide. Grade 2 tumors represent a good window of therapeutic intervention, whose optimization requires high resolution biomarker identification. Here we characterize energy metabolism and cellular properties associated with spreading and tumor progression of RT112 and 5637, two Grade 2 cancer cell lines derived from human bladder, representative of luminal-like and basal-like tumors, respectively. The two cell lines have similar proliferation rates, but only 5637 cells show efficient lateral migration. In contrast, RT112 cells are more prone to form spheroids. RT112 cells produce more ATP by glycolysis and OXPHOS, present overall higher metabolic plasticity and are less sensitive than 5637 to nutritional perturbation of cell proliferation and migration induced by treatment with 2-deoxyglucose and metformin. On the contrary, spheroid formation is less sensitive to metabolic perturbations in 5637 than RT112 cells. The ability of metformin to reduce, although with different efficiency, cell proliferation, sphere formation and migration in both cell lines, suggests that OXPHOS targeting could be an effective strategy to reduce the invasiveness of Grade 2 bladder cancer cells.https://www.mdpi.com/2073-4409/9/12/2669bladder cancerenergy and redox metabolismcellular bioenergeticsmitochondrial functionglycolysisfatty acids oxidation |
| spellingShingle | Valentina Pasquale Giacomo Ducci Gloria Campioni Adria Ventrici Chiara Assalini Stefano Busti Marco Vanoni Riccardo Vago Elena Sacco Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties Cells bladder cancer energy and redox metabolism cellular bioenergetics mitochondrial function glycolysis fatty acids oxidation |
| title | Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties |
| title_full | Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties |
| title_fullStr | Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties |
| title_full_unstemmed | Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties |
| title_short | Profiling and Targeting of Energy and Redox Metabolism in Grade 2 Bladder Cancer Cells with Different Invasiveness Properties |
| title_sort | profiling and targeting of energy and redox metabolism in grade 2 bladder cancer cells with different invasiveness properties |
| topic | bladder cancer energy and redox metabolism cellular bioenergetics mitochondrial function glycolysis fatty acids oxidation |
| url | https://www.mdpi.com/2073-4409/9/12/2669 |
| work_keys_str_mv | AT valentinapasquale profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT giacomoducci profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT gloriacampioni profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT adriaventrici profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT chiaraassalini profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT stefanobusti profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT marcovanoni profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT riccardovago profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties AT elenasacco profilingandtargetingofenergyandredoxmetabolismingrade2bladdercancercellswithdifferentinvasivenessproperties |