Duke Researchers Find Breast Cancer Cells Enter the Leptomeninges Via Bone Marrow and Emissary Veins

Duke researchers found that breast cancer cells are able to enter the leptomeninges, the cerebrospinal fluid (CSF) containing membranes that line the brain and the spinal cord, via bone marrow and the surface of emissary veins.

Science published “Breast cancer exploits neural signaling pathways for bone-to-meninges metastasis” on June 21, 2024.

Utilizing mouse models, the Sipkins Lab showed that breast cancer cells that expressed the cell surface receptor integrin alpha 6 were able to enter the leptomeninges along the outer surface of blood vessels that connect bone marrow from the nearby vertebrae and skull bones to the leptomeninges.

“Treatment outcomes for breast cancer metastasis to the leptomeninges are extremely poor,” Dorothy Sipkins, MD, PhD said.

While the leptomeninges are typically a harsh environment for cancer cell survival, the lab found that those breast cancer cells stimulated white blood cells to produce a pro-survival protein, glial-derived neurotrophic factor, that supports tumor growth.

Sipkins said that the findings “shed new light on tumor-host interactions in the leptomeninges.”

 “Leptomeningeal disease is a devastating form of cancer metastasis with few treatment options,” Sipkins said. “My lab is very excited to provide insights into the biology of this disease process and hope that our discoveries will lead to the development of novel therapies.”

Sipkins’ lab studies the molecular characteristics of tissue microenvironments, or “niches,” that regulate the migration, survival and regeneration of cancerous cells. Sipkins is the senior author of the paper as well as an associate professor of medicine, associate research professor in pharmacology and cancer biology, affiliate of the Duke Regeneration Center, and member of the Duke Center for Brain and Spine Metastasis and the Duke Cancer Institute.