Comparing the fate of brain metastatic breast cancer cells in different immune compromised mice with cellular magnetic resonance imaging

Abstract

Metastasis is the leading cause of mortality in breast cancer patients, with brain metastases becoming increasingly prevalent. Studying this disease is challenging due to the limited experimental models and methods available. Here, we used iron-based cellular MRI to track the fate of a mammary carcinoma cell line (MDA-MB-231-BR) in vivo to characterize the growth of brain metastases in the nude and severely immune-compromised NOD/SCID/ILIIrg-/-(NSG) mouse.Nude and NSG mice received injections of iron-labeled MDA-MB-231-BR cells. Images were acquired with a 3T MR system and assessed for signal voids and metastases. The percentage of signal voids and the number and volume of metastases were quantified. Ex vivo imaging of the liver, histology, and immunofluorescence labeling was performed.On day 0, iron-labeled cells were visualized as signal voids throughout the brain. The percentage of voids decreased significantly between day 0 and endpoint. At endpoint, there was no difference in the number of brain metastases or tumour burden in NSG mice compared to nudes. Tumour volumes in nude mice were significantly larger than in NSG mice. Body images indicated that the NSG mice had metastases in the liver, lungs, and lymph nodes.Characterization of the NSG and nude mouse is necessary to study breast cancer brain metastasis in vivo. Here, we show that the 231BR cell line grew differently in NSG mice compared to nude mice. This work demonstrates the role that imaging can play toward credentialing these models that cannot be done with other in vitro or histopathologic methods alone.

Preclinical Models of Brain Metastases in Breast Cancer

“…Finally, most of the models are based on the utilization of immune-compromised mice and thus lack the immune components of the tumor microenvironment that are essential for tumor colonization and progression [68,124]. The importance of the tumor microenvironment in the brain can also be gauged from the fact that the same cancer cell line may exhibit differential growth characteristics depending on the strain of the mouse used for cell line establishment [125]. These differences could be explained by the differences in immune competency of each strain, such as the lack of T cells in nude mice compared to the lack of T, NK, and B cells and defective macrophages and dendritic cells in the severely immune compromised NSG mouse.…”

An Insight into Molecular Targets of Breast Cancer Brain Metastasis

“…The incidence of brain metastases seems to have increased in recent years, likely due to the prolonged survival of patients receiving effective treatments and the availability of better imaging techniques that lead to improved detection of brain metastases [ 19 , 22 ]. Table 1 summarizes different risk factors, their identification, and chances of BM in BC patients.…”