Open AccessCharacterization of the melanoma brain metastatic niche in mice and humans
Author(s) -
Amit Moran,
LaiderTrejo Leonor,
Shalom Vardit,
ShabtayOrbach Ayelet,
Krelin Yakov,
Gil Ziv
Publication year - 2013
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.45
Subject(s) - melanoma , stromal cell , intracardiac injection , pathology , metastasis , in vivo , infiltration (hvac) , parenchyma , brain metastasis , medicine , immunofluorescence , human brain , biology , cancer research , cancer , antibody , immunology , physics , microbiology and biotechnology , psychiatry , thermodynamics
Brain metastases occur in 15% of patients with melanoma and are associated with a dismal prognosis. Here, we investigate the architectural phenotype and stromal reaction of melanoma brain metastasis in mice and humans. A syngeneic, green fluorescence protein ( GFP )‐expressing murine B16‐F1 melanoma clone was introduced via intracardiac injection, and was examined in vivo in comparison with human specimens. Immunofluorescence analyses of the brain metastases revealed that F4/80 + macrophages/microglia were most abundant at the tumor front, but rare in its core, where they were found only around blood vessels ( P = 0.01). Similar pattern of infiltration was found in CD 3 + T cells ( P < 0.01). Infiltrating T cells were prominently CD 4 + compared with CD 8 + T cells ( P < 0.001). Blood vessels ( CD 31 + ) were less abundant at the tumor front than in its center (12 ± 1 vs. 4 ± 0.6 vessels per high‐power field [ HPF ], P < 0.001). In contrast, there were few vessels at the tumor front, but their diameter was significantly larger at the front (8236 μm 2 vs. 4617 μm 2 average cross‐sectional area, P < 0.005). This is the first comparative analysis of melanoma brain metastases showing similar stromal reaction in murine models and human specimens. Our results validate the utility of this murine model of melanoma brain metastases for investigating the mechanism of the human disease.