Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin

Abstract Background Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum. Methods We established animal models by injecting intracardially in athymic nude fox1nu mice two human melanoma cell lines, ori...

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Autores principales:	Henrik A. Svendsen, Torstein R. Meling, Vigdis Nygaard, Stein Waagene, Hege Russnes, Siri Juell, Siril G. Rogne, Jens Pahnke, Eirik Helseth, Øystein Fodstad, Gunhild M. Mælandsmo
Formato:	article
Lenguaje:	EN
Publicado:	Wiley 2021
Materias:	athymic nude fox1nu mice brain metastasis model human melanoma site specificity tissue‐specific metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/f55513056da94b4b9656792ae72ff8df
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spelling	oai:doaj.org-article:f55513056da94b4b9656792ae72ff8df2021-12-01T04:49:16ZNovel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin2045-763410.1002/cam4.4334https://doaj.org/article/f55513056da94b4b9656792ae72ff8df2021-12-01T00:00:00Zhttps://doi.org/10.1002/cam4.4334https://doaj.org/toc/2045-7634Abstract Background Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum. Methods We established animal models by injecting intracardially in athymic nude fox1nu mice two human melanoma cell lines, originating from a cerebral metastasis (HM19) and a cerebellar metastasis (HM86). Results Using magnetic resonance imaging (MRI), metastases were first detected after a mean of 34.5 days. Mean survival time was 59.6 days for the mice in the HM86 group and significantly shorter (43.7 days) for HM19‐injected animals (p < 0.001). In the HM86 group, the first detectable metastasis was located in the cerebellum in 15/55 (29%) mice compared with none in the HM19 group (p < 0.001). At sacrifice, cerebellar metastases were found in 34/55 (63%) HM86‐injected mice compared with 1/53 (2%) in the HM19‐injected (p < 0.001) mice. At that time, all mice in both groups had detectable metastases in the cerebrum. Comparing macroscopic and histologic appearances of the brain metastases with their clinical counterparts, the cell line‐based tumors had kept their original morphologic characteristics. Conclusions The present work demonstrates that human brain‐metastatic melanoma cells injected intracardially in mice had retained inherent characteristics also in reproducing interaction with subtle microenvironmental brain tissue compartment‐specific features. The models offer new possibilities for investigating tumor‐ and host‐associated factors involved in determining tissue specificity of brain metastasis.Henrik A. SvendsenTorstein R. MelingVigdis NygaardStein WaageneHege RussnesSiri JuellSiril G. RogneJens PahnkeEirik HelsethØystein FodstadGunhild M. MælandsmoWileyarticleathymic nude fox1nu micebrain metastasis modelhuman melanomasite specificitytissue‐specific metastasisNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancer Medicine, Vol 10, Iss 23, Pp 8604-8613 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	athymic nude fox1nu mice brain metastasis model human melanoma site specificity tissue‐specific metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	athymic nude fox1nu mice brain metastasis model human melanoma site specificity tissue‐specific metastasis Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Henrik A. Svendsen Torstein R. Meling Vigdis Nygaard Stein Waagene Hege Russnes Siri Juell Siril G. Rogne Jens Pahnke Eirik Helseth Øystein Fodstad Gunhild M. Mælandsmo Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
description	Abstract Background Malignant melanomas frequently metastasize to the brain, but metastases in the cerebellum are underrepresented compared with metastases in the cerebrum. Methods We established animal models by injecting intracardially in athymic nude fox1nu mice two human melanoma cell lines, originating from a cerebral metastasis (HM19) and a cerebellar metastasis (HM86). Results Using magnetic resonance imaging (MRI), metastases were first detected after a mean of 34.5 days. Mean survival time was 59.6 days for the mice in the HM86 group and significantly shorter (43.7 days) for HM19‐injected animals (p < 0.001). In the HM86 group, the first detectable metastasis was located in the cerebellum in 15/55 (29%) mice compared with none in the HM19 group (p < 0.001). At sacrifice, cerebellar metastases were found in 34/55 (63%) HM86‐injected mice compared with 1/53 (2%) in the HM19‐injected (p < 0.001) mice. At that time, all mice in both groups had detectable metastases in the cerebrum. Comparing macroscopic and histologic appearances of the brain metastases with their clinical counterparts, the cell line‐based tumors had kept their original morphologic characteristics. Conclusions The present work demonstrates that human brain‐metastatic melanoma cells injected intracardially in mice had retained inherent characteristics also in reproducing interaction with subtle microenvironmental brain tissue compartment‐specific features. The models offer new possibilities for investigating tumor‐ and host‐associated factors involved in determining tissue specificity of brain metastasis.
format	article
author	Henrik A. Svendsen Torstein R. Meling Vigdis Nygaard Stein Waagene Hege Russnes Siri Juell Siril G. Rogne Jens Pahnke Eirik Helseth Øystein Fodstad Gunhild M. Mælandsmo
author_facet	Henrik A. Svendsen Torstein R. Meling Vigdis Nygaard Stein Waagene Hege Russnes Siri Juell Siril G. Rogne Jens Pahnke Eirik Helseth Øystein Fodstad Gunhild M. Mælandsmo
author_sort	Henrik A. Svendsen
title	Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
title_short	Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
title_full	Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
title_fullStr	Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
title_full_unstemmed	Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin
title_sort	novel human melanoma brain metastasis models in athymic nude fox1nu mice: site‐specific metastasis patterns reflecting their clinical origin
publisher	Wiley
publishDate	2021
url	https://doaj.org/article/f55513056da94b4b9656792ae72ff8df
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Novel human melanoma brain metastasis models in athymic nude fox1nu mice: Site‐specific metastasis patterns reflecting their clinical origin

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