Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma
INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple l...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2016-06-01
|
| Series: | Translational Oncology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1936523316300109 |
| _version_ | 1818614432923648000 |
|---|---|
| author | Trude G. Simonsen Jon-Vidar Gaustad Einar K. Rofstad |
| author_facet | Trude G. Simonsen Jon-Vidar Gaustad Einar K. Rofstad |
| author_sort | Trude G. Simonsen |
| collection | DOAJ |
| description | INTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases. |
| first_indexed | 2024-12-16T16:17:56Z |
| format | Article |
| id | doaj.art-15a2519beabb4ee0965829bca14aa505 |
| institution | Directory Open Access Journal |
| issn | 1936-5233 1944-7124 |
| language | English |
| last_indexed | 2024-12-16T16:17:56Z |
| publishDate | 2016-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Translational Oncology |
| spelling | doaj.art-15a2519beabb4ee0965829bca14aa5052022-12-21T22:25:01ZengElsevierTranslational Oncology1936-52331944-71242016-06-019321121810.1016/j.tranon.2016.04.003Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant MelanomaTrude G. SimonsenJon-Vidar GaustadEinar K. RofstadINTRODUCTION: A majority of patients with melanoma brain metastases develop multiple lesions, and these patients show particularly poor prognosis. To develop improved treatment strategies, detailed insights into the biology of melanoma brain metastases, and particularly the development of multiple lesions, are needed. The purpose of this preclinical investigation was to study melanoma cell migration within the brain after cell injection into a well-defined intracerebral site. METHODS: A-07, D-12, R-18, and U-25 human melanoma cells transfected with green fluorescent protein were injected stereotactically into the right cerebral hemisphere of nude mice. Moribund mice were killed and autopsied, and the brain was evaluated by fluorescence imaging or histological examination. RESULTS: Intracerebral inoculation of melanoma cells produced multiple lesions involving all regions of the brain, suggesting that the cells were able to migrate over substantial distances within the brain. Multiple modes of transport were identified, and all transport modes were observed in all four melanoma lines. Thus, the melanoma cells were passively transported via the flow of cerebrospinal fluid in the meninges and ventricles, they migrated actively along leptomeningeal and brain parenchymal blood vessels, and they migrated actively along the surfaces separating different brain compartments. CONCLUSION: Migration of melanoma cells after initial arrest, extravasation, and growth at a single location within the brain may contribute significantly to the development of multiple melanoma brain metastases.http://www.sciencedirect.com/science/article/pii/S1936523316300109 |
| spellingShingle | Trude G. Simonsen Jon-Vidar Gaustad Einar K. Rofstad Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma Translational Oncology |
| title | Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma |
| title_full | Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma |
| title_fullStr | Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma |
| title_full_unstemmed | Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma |
| title_short | Intracranial Tumor Cell Migration and the Development of Multiple Brain Metastases in Malignant Melanoma |
| title_sort | intracranial tumor cell migration and the development of multiple brain metastases in malignant melanoma |
| url | http://www.sciencedirect.com/science/article/pii/S1936523316300109 |
| work_keys_str_mv | AT trudegsimonsen intracranialtumorcellmigrationandthedevelopmentofmultiplebrainmetastasesinmalignantmelanoma AT jonvidargaustad intracranialtumorcellmigrationandthedevelopmentofmultiplebrainmetastasesinmalignantmelanoma AT einarkrofstad intracranialtumorcellmigrationandthedevelopmentofmultiplebrainmetastasesinmalignantmelanoma |