Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts
Abstract Background Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6–9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (β-ala...
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| Format: | Article |
| Language: | English |
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BMC
2018-08-01
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| Series: | Cancer Cell International |
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| Online Access: | http://link.springer.com/article/10.1186/s12935-018-0611-2 |
| _version_ | 1819120628426342400 |
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| author | Henry Oppermann Johannes Dietterle Katharina Purcz Markus Morawski Christian Eisenlöffel Wolf Müller Jürgen Meixensberger Frank Gaunitz |
| author_facet | Henry Oppermann Johannes Dietterle Katharina Purcz Markus Morawski Christian Eisenlöffel Wolf Müller Jürgen Meixensberger Frank Gaunitz |
| author_sort | Henry Oppermann |
| collection | DOAJ |
| description | Abstract Background Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6–9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (β-alanine-l-histidine), which has an inhibitory effect on glioblastoma proliferation, may on the opposite promote invasion as proposed by the so-called “go-or-grow concept”. Methods Cell viability of nine patient derived primary (isocitrate dehydrogenase wildtype; IDH1R132H non mutant) glioblastoma cell cultures and of eleven patient derived fibroblast cultures was determined by measuring ATP in cell lysates and dehydrogenase activity after incubation with 0, 50 or 75 mM carnosine for 48 h. Using the glioblastoma cell line T98G, patient derived glioblastoma cells and fibroblasts, a co-culture model was developed using 12 well plates and cloning rings, placing glioblastoma cells inside and fibroblasts outside the ring. After cultivation in the presence of carnosine, the number of colonies and the size of the tumor cell occupied area were determined. Results In 48 h single cultures of fibroblasts and tumor cells, 50 and 75 mM carnosine reduced ATP in cell lysates and dehydrogenase activity when compared to the corresponding untreated control cells. Co-culture experiments revealed that after 4 week exposure to carnosine the number of T98G tumor cell colonies within the fibroblast layer and the area occupied by tumor cells was reduced with increasing concentrations of carnosine. Although primary cultured tumor cells did not form colonies in the absence of carnosine, they were eliminated from the co-culture by cell death and did not build colonies under the influence of carnosine, whereas fibroblasts survived and were healthy. Conclusions Our results demonstrate that the anti-proliferative effect of carnosine is not accompanied by an induction of cell migration. Instead, the dipeptide is able to prevent colony formation and selectively eliminates tumor cells in a co-culture with fibroblasts. |
| first_indexed | 2024-12-22T06:23:41Z |
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| id | doaj.art-f42941191f62464a828cfcf6c74b6694 |
| institution | Directory Open Access Journal |
| issn | 1475-2867 |
| language | English |
| last_indexed | 2024-12-22T06:23:41Z |
| publishDate | 2018-08-01 |
| publisher | BMC |
| record_format | Article |
| series | Cancer Cell International |
| spelling | doaj.art-f42941191f62464a828cfcf6c74b66942022-12-21T18:35:53ZengBMCCancer Cell International1475-28672018-08-0118111010.1186/s12935-018-0611-2Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblastsHenry Oppermann0Johannes Dietterle1Katharina Purcz2Markus Morawski3Christian Eisenlöffel4Wolf Müller5Jürgen Meixensberger6Frank Gaunitz7Department of Neurosurgery, University Hospital LeipzigDepartment of Neurosurgery, University Hospital LeipzigDepartment of Neurosurgery, University Hospital LeipzigMedical Faculty, Paul-Flechsig-Institute of Brain Research, University of LeipzigDepartment of Neuropathology, University Hospital LeipzigDepartment of Neuropathology, University Hospital LeipzigDepartment of Neurosurgery, University Hospital LeipzigDepartment of Neurosurgery, University Hospital LeipzigAbstract Background Glioblastoma (GBM) is a tumor of the central nervous system. After surgical removal and standard therapy, recurrence of tumors is observed within 6–9 months because of the high migratory behavior and the infiltrative growth of cells. Here, we investigated whether carnosine (β-alanine-l-histidine), which has an inhibitory effect on glioblastoma proliferation, may on the opposite promote invasion as proposed by the so-called “go-or-grow concept”. Methods Cell viability of nine patient derived primary (isocitrate dehydrogenase wildtype; IDH1R132H non mutant) glioblastoma cell cultures and of eleven patient derived fibroblast cultures was determined by measuring ATP in cell lysates and dehydrogenase activity after incubation with 0, 50 or 75 mM carnosine for 48 h. Using the glioblastoma cell line T98G, patient derived glioblastoma cells and fibroblasts, a co-culture model was developed using 12 well plates and cloning rings, placing glioblastoma cells inside and fibroblasts outside the ring. After cultivation in the presence of carnosine, the number of colonies and the size of the tumor cell occupied area were determined. Results In 48 h single cultures of fibroblasts and tumor cells, 50 and 75 mM carnosine reduced ATP in cell lysates and dehydrogenase activity when compared to the corresponding untreated control cells. Co-culture experiments revealed that after 4 week exposure to carnosine the number of T98G tumor cell colonies within the fibroblast layer and the area occupied by tumor cells was reduced with increasing concentrations of carnosine. Although primary cultured tumor cells did not form colonies in the absence of carnosine, they were eliminated from the co-culture by cell death and did not build colonies under the influence of carnosine, whereas fibroblasts survived and were healthy. Conclusions Our results demonstrate that the anti-proliferative effect of carnosine is not accompanied by an induction of cell migration. Instead, the dipeptide is able to prevent colony formation and selectively eliminates tumor cells in a co-culture with fibroblasts.http://link.springer.com/article/10.1186/s12935-018-0611-2GlioblastomaMigration assayFibroblast ring co-cultureCarnosine |
| spellingShingle | Henry Oppermann Johannes Dietterle Katharina Purcz Markus Morawski Christian Eisenlöffel Wolf Müller Jürgen Meixensberger Frank Gaunitz Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts Cancer Cell International Glioblastoma Migration assay Fibroblast ring co-culture Carnosine |
| title | Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts |
| title_full | Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts |
| title_fullStr | Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts |
| title_full_unstemmed | Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts |
| title_short | Carnosine selectively inhibits migration of IDH-wildtype glioblastoma cells in a co-culture model with fibroblasts |
| title_sort | carnosine selectively inhibits migration of idh wildtype glioblastoma cells in a co culture model with fibroblasts |
| topic | Glioblastoma Migration assay Fibroblast ring co-culture Carnosine |
| url | http://link.springer.com/article/10.1186/s12935-018-0611-2 |
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