Glioblastoma study findings: Brain cell ‘crosstalk’ and cancer growth; Preoperative radiotherapy may enhance survival

By Lynda De Widt

Brain cell ‘crosstalk’ leads to elevated proteins and cancer growth

Already the most aggressive form of brain cancer, glioblastoma can become even more deadly when it arises near the brain's C-shaped, fluid-filled cavities called the lateral ventricles. 

What makes this type of tumor so aggressive? In a new study published in Science Advances, Mayo Clinic researchers set out to answer this question.

First, the scientists developed a preclinical model in which they fluorescently labeled proteins produced by neural stem cells. With the help of the fluorescence, which colorfully highlights different parts of cells, the scientists could see that glioblastoma-induced senescence, or premature aging, of neural stem cells located in the lateral ventricles, could promote tumor growth.

Next, they looked at glioblastoma cell cultures and discovered that these cells produce elevated amounts of a tumor-promoting protein called cathepsin b (CTSB), which is associated with a worse prognosis for patients.

Through a battery of experiments, the team found that the CTSB protein contributes to increased glioblastoma malignancy. They observed this consistently in cell cultures, animal models and tumor tissue samples — particularly in lateral ventricle-associated tumors — from patients who donated to the Mayo Clinic Neurosurgery BRIDGE Biobank and The Cancer Genome Atlas.

The team hypothesizes that "crosstalk," or communication between neural stem cells and glioblastoma tumors, leads to CTSB protein expression.

"Our findings give us better insight into the biology of glioblastoma, which is essential to finding a treatment or cure for this deadly disease," says senior author Hugo Guerrero Cazares, M.D., Ph.D., associate professor of neurosurgery, cancer biology and neuroscience and leader of the Neurogenesis and Brain Tumors Lab at Mayo Clinic in Florida. Dr. Guerrero Cazares also is vice chair of research in the Neurosurgery Department.

The scientists next plan to build on their findings in two ways: First is identifying proteins or other molecules released by lateral ventricle cells that cause glioblastoma tumors to express CTSB. Second is conducting preclinical studies to target CTSB with pharmaceutical compounds.

Preoperative radiotherapy for glioblastoma enhances survival in a preclinical model

Preoperative radiotherapy is commonly used to treat different cancers that have spread to the brain but has never been used in primary glioblastoma, or cancer that originates in the brain.

Since 2005, the standard of care for glioblastoma has been surgical removal of the tumor, followed by radiation and chemotherapy. Even with this aggressive treatment approach, survival is poor — on average, just under 15 months. This poor outcome is often due to incomplete elimination of the cancer cells, cancer recurrence and the tumor's acquired resistance to therapies. In many patients with newly diagnosed glioblastoma, brain tumors recur immediately after surgery and before chemotherapy is administered.

In a study published in the Journal of Neuro-Oncology, Mayo Clinic researchers found that using a radiation boost before surgery increased survival in a preclinical glioblastoma model, compared to postoperative radiation. The study also sheds light on how this approach impacts the tumor microenvironment—the cellular environment in which a tumor exists—specifically highlighting changes in cell senescence and the movement of cancer-attacking cells to the tumor. The researchers say these insights not only advance the understanding of glioblastoma biology but also propose a pioneering therapeutic approach that could one day benefit patients facing this challenging cancer.

"Our research challenges the conventional treatment sequence and suggests a potentially more effective strategy for managing glioblastoma," says senior study author Paula Schiapparelli, Ph.D., a neurosurgery researcher at Mayo Clinic.

First author Beatriz Fernandez-Gil, Ph.D., says additional laboratory studies and clinical trials are needed to confirm the team's results. Scientists plan to study stereotactic radiosurgery before tumor removal, followed by standard-of-care radiotherapy.

Learn more

Learn more about glioblastoma and find a clinical trial at Mayo Clinic.

Join the Brain Tumor Support Group on Mayo Clinic Connect, an online community moderated by Mayo Clinic for patients and caregivers.

Also, read these articles:

• Treatment and research of glioblastoma
• Fighting glioblastoma — one of the deadliest forms of brain cancer

This article is an excerpt from an article originally published on the Mayo Clinic News Network.