Brain metastasis occurs when cancer cells that form in the breast, lung or other tissues, spread to the brain. It’s estimated that up to 20% of all cancer patients exhibit brain metastases, which come in two main types: parenchymal metastases, which grow within the brain itself, and leptomeningeal metastases (LM), which grow in the membranes that surround the brain and spinal cord. LM are associated with a very poor prognosis, with median survival of treated patients being less than 3 months. LM are largely understudied by the research community due to a lack of animal models. Since 2019, GCI graduate student Rima focuses her studies on establishing factors that allow cancer cells to spread to and survive in the brain and spinal cord.
In collaboration with Prof. Morag Park’s lab, the Siegel lab has successfully established the first patient-derived xenograft (PDX) model that spontaneously forms LM from tumors grown in the mouse breast. “Such a model is exceedingly rare, and we aren’t aware of any published papers that describe breast cancer cells capable of spreading specifically to the leptomeninges from the primary site,” shares Rima.
Her work does not stop there: Rima’s in-depth analysis of this model revealed an increase in expression of a protein called CIRBP (Cold Inducible RNA Binding Protein) in LM, hypothesizing it to be a critical mediator that allows cancer cells to reach and survive in the leptomeninges. She continues to characterize the role of CIRBP in facilitating breast cancer metastasis to the leptomeninges and identifying its targets in this process. “For this purpose, I use breast cancer cell lines, our PDX that forms LM and immunocompromised mice. The knowledge gained from my project may ultimately contribute to the prevention or treatment of LM, which are associated with an extremely poor prognosis for thousands of cancer patients annually.”
To accomplish this, Rima is actively collaborating with members from lab of Prof. Marc Fabian at the Lady Davis Institute to identify the mRNA targets of CIRBP. She is also supported by several Scientific Platforms at the GCI, including McGill Integrated Core for Animal Modeling (MICAM), Histology Innovation Platform and the Advanced Bioimaging Family (ABIF) at McGill University. “Having the facilities located within the GCI allows for easy access and saves time. The staff are nice and helpful. They assist trainees in getting trained to use their equipment, in troubleshooting whenever needed and in data analysis when applicable.”