Breast cancer brain metastasis development induced by intracarotid injection of MDA-MB 231 human breast cancer cells in mice
Autors:
Romain Roth Dit Bettoni, Nicolas Hoffmann, Jordan Longin, Peggy Provent, Ismahene Benzaid, Marc Hillairet De Boisferon
Abstract :
Breast cancer is the most common malignancy in women worldwide. Breast cancer can be divided into four types based on molecular subtypes: luminal A, luminal B, human epidermal growth factor receptor 2 (Her2) positive, and triple negative breast cancer (TNBC). These subtypes have very different prognoses and treatment methods.
Herceptin, a treatment specifically directed against Her2 (overexpressed in 20–25% of breast cancers), has been widely used and improves the prognosis for Her2-positive breast cancer. TNBC accounts for only 15–20% of breast cancers and is considered as the most aggressive breast cancer. This subtype does not express estrogen receptor (ER), progesterone receptor (PR), and Her2. Additionally, it is usually identified at an advanced stage of cancer progression and often results in metastases to the brain, bones, lungs, and liver.
Human subcutaneous tumors represent a small fraction of cancers that are easy to treat by surgery and chemotherapy and are technically easy to recapitulate inanimals. In contrast, high grade breast cancer and metastases represent a leading cause of cancer-related mortality for which more relevant animal tumor models arerequired. Additionally, the poor prognosis of metastases is badly increased in the brain, particularly due to the difficulty for novel therapies to overcome the bloodbrain barrier. There are very few animal models exclusively focused on the development of brain metastases, and most are based on stereotactic intracranialinoculation of cells. This injection mode rather mimics the onset of primary tumors than metastases, as it leads to the formation of single tumors and does not recapitulate the extravasation and seeding events of the metastatic cascade.
In this poster we show a new TNBC mouse model of brain metastasis. We induced brain metastases by intracarotid injection of TNBC cells, thus recapitulating thetumor cells’ pathway to the brain. We evaluated the metastases progression by morphological T2 weighted MRI imaging. In parallel, we assessed the blood brainbarrier integrity by T1 weighted imaging after Gd-DOTA injections and followed edema formation by FLAIR MRI.
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