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

Cancer Med. 2021 Dec;10(23):8604-8613. doi: 10.1002/cam4.4334. Epub 2021 Oct 6.


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.

Keywords: athymic nude fox1nu mice; brain metastasis model; human melanoma; site specificity; tissue-specific metastasis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain Neoplasms / diagnostic imaging
  • Brain Neoplasms / secondary*
  • Cell Line, Tumor
  • Disease Models, Animal
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Melanoma / diagnostic imaging
  • Melanoma / secondary*
  • Mice, Nude
  • Neoplasm Metastasis
  • Skin Neoplasms / pathology*
  • Tumor Cells, Cultured