A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection
Background: Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will need to target the specific biology of tumour recurrence, but our current understanding of the underlying mechanisms i...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2024-01-01
|
| Series: | Cells |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2073-4409/13/2/192 |
| _version_ | 1797339952592191488 |
|---|---|
| author | Thomas M. B. Ware Rodney B. Luwor Hong-Jian Zhu |
| author_facet | Thomas M. B. Ware Rodney B. Luwor Hong-Jian Zhu |
| author_sort | Thomas M. B. Ware |
| collection | DOAJ |
| description | Background: Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will need to target the specific biology of tumour recurrence, but our current understanding of the underlying mechanisms is limited. Significantly, there is a lack of available methods and models that are tailored to the examination of tumour recurrence. Methods: NOD-SCID mice were orthotopically implanted with luciferase-labelled donor U87MG or MU20 glioblastoma cells. Four days later, an unlabelled recipient tumor was implanted on the contralateral side. The mice were euthanised at a humane end-point and tissue and blood samples were collected for ex vivo analyses. Results: The ex vivo analyses of the firefly-labelled MU20 tumours displayed extensive invasion at the primary tumour margins, whereas the firefly-labelled U87MG tumours exhibited expansive phenotypes with no evident invasions at the tumour margins. Luciferase signals were detected in the contralateral unlabelled recipient tumours for both the U87MG and MU20 tumours compared to the non-implanted control brain. Remarkably, tumour cells were uniformly detected in all tissue samples of the supratentorial brain region compared to the control tissue, with single tumour cells detected in some tissue samples. Circulating tumour cells were also detected in the blood samples of most of the xenografted mice. Moreover, tumour cells were detected in the lungs of all of the mice, a probable event related to haematogenous dissemination. Similar results were obtained when the U87MG cells were alternatively labelled with gaussian luciferase. Conclusions: These findings describe a systemic disease model for glioblastoma which can be used to investigate recurrence biology and therapeutic efficacy towards recurrence. |
| first_indexed | 2024-03-08T09:56:00Z |
| format | Article |
| id | doaj.art-959993cf85e84517a64d3e2785b4e150 |
| institution | Directory Open Access Journal |
| issn | 2073-4409 |
| language | English |
| last_indexed | 2024-03-08T09:56:00Z |
| publishDate | 2024-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cells |
| spelling | doaj.art-959993cf85e84517a64d3e2785b4e1502024-01-29T13:50:39ZengMDPI AGCells2073-44092024-01-0113219210.3390/cells13020192A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell DetectionThomas M. B. Ware0Rodney B. Luwor1Hong-Jian Zhu2Department of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaDepartment of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaDepartment of Surgery, The Royal Melbourne Hospital, The University of Melbourne, Parkville, VIC 3050, AustraliaBackground: Glioblastoma is characterised by extensive infiltration into the brain parenchyma, leading to inevitable tumor recurrence and therapeutic failure. Future treatments will need to target the specific biology of tumour recurrence, but our current understanding of the underlying mechanisms is limited. Significantly, there is a lack of available methods and models that are tailored to the examination of tumour recurrence. Methods: NOD-SCID mice were orthotopically implanted with luciferase-labelled donor U87MG or MU20 glioblastoma cells. Four days later, an unlabelled recipient tumor was implanted on the contralateral side. The mice were euthanised at a humane end-point and tissue and blood samples were collected for ex vivo analyses. Results: The ex vivo analyses of the firefly-labelled MU20 tumours displayed extensive invasion at the primary tumour margins, whereas the firefly-labelled U87MG tumours exhibited expansive phenotypes with no evident invasions at the tumour margins. Luciferase signals were detected in the contralateral unlabelled recipient tumours for both the U87MG and MU20 tumours compared to the non-implanted control brain. Remarkably, tumour cells were uniformly detected in all tissue samples of the supratentorial brain region compared to the control tissue, with single tumour cells detected in some tissue samples. Circulating tumour cells were also detected in the blood samples of most of the xenografted mice. Moreover, tumour cells were detected in the lungs of all of the mice, a probable event related to haematogenous dissemination. Similar results were obtained when the U87MG cells were alternatively labelled with gaussian luciferase. Conclusions: These findings describe a systemic disease model for glioblastoma which can be used to investigate recurrence biology and therapeutic efficacy towards recurrence.https://www.mdpi.com/2073-4409/13/2/192glioblastomaorthotopic mouse modelsingle-cell detection |
| spellingShingle | Thomas M. B. Ware Rodney B. Luwor Hong-Jian Zhu A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection Cells glioblastoma orthotopic mouse model single-cell detection |
| title | A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection |
| title_full | A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection |
| title_fullStr | A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection |
| title_full_unstemmed | A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection |
| title_short | A New Systemic Disease Mouse Model for Glioblastoma Capable of Single-Tumour-Cell Detection |
| title_sort | new systemic disease mouse model for glioblastoma capable of single tumour cell detection |
| topic | glioblastoma orthotopic mouse model single-cell detection |
| url | https://www.mdpi.com/2073-4409/13/2/192 |
| work_keys_str_mv | AT thomasmbware anewsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection AT rodneybluwor anewsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection AT hongjianzhu anewsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection AT thomasmbware newsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection AT rodneybluwor newsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection AT hongjianzhu newsystemicdiseasemousemodelforglioblastomacapableofsingletumourcelldetection |