1. Novel human melanoma brain metastasis models in athymic nude fox1 nu mice: Site‐specific metastasis patterns reflecting their clinical origin
- Author
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Vigdis Nygaard, Jens Pahnke, Siril G. Rogne, Stein Waagene, Gunhild Mari Mælandsmo, Torstein R. Meling, Øystein Fodstad, Siri Juell, Eirik Helseth, Hege G. Russnes, and Henrik A Svendsen
- Subjects
Cancer Research ,Cerebellum ,Pathology ,medicine.medical_specialty ,site specificity ,Metastasis ,030207 dermatology & venereal diseases ,03 medical and health sciences ,brain metastasis model ,0302 clinical medicine ,medicine ,Human melanoma ,Radiology, Nuclear Medicine and imaging ,neoplasms ,RC254-282 ,tissue‐specific metastasis ,Athymic nude fox1nu mice ,medicine.diagnostic_test ,business.industry ,Cerebrum ,Melanoma ,Site specificity ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,Magnetic resonance imaging ,Brain metastasis model ,medicine.disease ,nervous system diseases ,ddc:616.8 ,3. Good health ,athymic nude fox1nu mice ,medicine.anatomical_structure ,nervous system ,Oncology ,Cell culture ,030220 oncology & carcinogenesis ,Tissue- specific metastasis ,business ,human melanoma ,Brain metastasis - 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.
- Published
- 2021