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Brain metastasis model in athymic nude mice using a novel MUC1-secreting human breast-cancer cell line, MA11

✍ Scribed by Phil D. Rye; Lars Norum; Dag-Rune Olsen; Solveig Garman-Vik; Sepp Kaul; Østein Fodstad


Publisher
John Wiley and Sons
Year
1996
Tongue
French
Weight
776 KB
Volume
68
Category
Article
ISSN
0020-7136

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✦ Synopsis


The MA1 I human breast-cancer cell line was established with cells isolated from a bone-marrow sam le using immunomagnetic beads conjugated to the anti-MUt!I antibody BM-2. The cell line showed a selective preference for metastasising to the brain in athymic nude mice. Following injection of MA1 I cells into the left ventricle of the heart, brain metastases developed in 87% (20/23) animals, with a mean latency until development of neurological symptoms of 65 days. Necropsy and histological examination revealed tumour nodules of varying sizes throughout the brain, invading both grey and white matter of both hemispheres, and with extensive involvement of the cerebellum. MRI spin-echo images indicated brain lesions in some animals that were subsequently confirmed by histology. Three mice showed small tumour nodules (1-2 mm) in the lung, and 2 had solitary lesions (< I mm) within the spinal cord. Metastases were not detected in bone, liver, adrenal gland, kidney, spleen or heart. The human MUCl mucin, as determined by a europium-based immunoradiometric assay, was detected in the serum of 9 / I I animals that showed histological evidence of brain metastases. The much could not be found in mouse serum samples taken before day 46. The concentration range of MUC I observed was from < I to 250 U/ml, and did not appear to correlate with the size or number of tumours as determined from histological sections. This new model provides an opportunity to study the mechanisms of clinically relevant organselective metastases and may be of use in evaluating novel treatment for brain metastases in breast cancer.