A model of breast cancer meningeal metastases: characterization with in vivo molecular imaging.
Darshini KuruppuDeepak BhereChristian T FarrarKhalid ShahAnna-Liisa BrownellKenneth K TanabePublished in: Cancer gene therapy (2018)
Meningeal metastasis is a fatal complication of breast cancer which affects 8-15% of patients who experience severe neurological complications of cranial nerves, cerebrum, and spinal cord. Survival once diagnosed is less than 4 months. Currently there is no cure. Aggressive multimodal radiation, intra-CSF, or systemic chemotherapy is palliative. Investigation of urgently needed new treatment modalities is hindered by the lack of suitable animal models to effectively study tumor growth kinetics. We present a model of meningeal metastases where tumor growth and associated neurological symptoms have been characterized over 3 weeks by sequential molecular imaging, tumor growth kinetics, and histopathology. Meningeal metastases were induced by stereotaxic injection of human breast cancer cells (MDA-MB-231-Rluc) into the lateral ventricle. Tumor identified by Gd-MRI and Rluc-bioluminescence depict growth in 3 phases, namely lag, exponential, and plateau phase. Invasive tumor growth was highlighted by changes in contrast distribution in the meninges, ventricle and brain compartments over time where moderate contrast uptake in the early growth phase gave rise to a heavy tumor burden in the base of the brain in the latter phases. Tumor growth was accompanied with debilitating neurological symptoms and change in body mass. Tumor was confirmed by ex vivo histology. The reliability of the model to study novel therapeutics was confirmed by oncolytic virus delivered into the lateral ventricle showed potential for treatment. This effective and reliable model resembles human disease progression and is ideally suited to investigate novel treatments.
Keyphrases
- breast cancer cells
- spinal cord
- endothelial cells
- magnetic resonance
- pulmonary hypertension
- pulmonary artery
- cerebral ischemia
- mitral valve
- white matter
- spinal cord injury
- contrast enhanced
- minimally invasive
- multiple sclerosis
- induced pluripotent stem cells
- resting state
- small molecule
- young adults
- radiation therapy
- pulmonary arterial hypertension
- squamous cell carcinoma
- physical activity
- heart failure
- congenital heart disease
- rectal cancer
- risk assessment
- brain injury
- depressive symptoms
- cell death
- blood brain barrier
- climate change
- sleep quality
- quantum dots
- smoking cessation
- gestational age