Protein from blood vessel cells helps glioblastoma grow: Study
Pathway could be target for treatment, researchers say
A signaling molecule released by blood vessel cells prompts cancer cells to grow and become resistant to treatment in glioblastoma, an aggressive type of glioma, a study found.
Data suggest that this signaling pathway could be a useful target for treating glioblastoma, according to the study, “Endothelial-secreted Endocan activates PDGFRA and regulates vascularity and spatial phenotype in glioblastoma,” which was published in Nature Communications.
Glioblastoma is an aggressive type of brain tumor caused by the uncontrolled growth of astrocytes, a type of brain cell that normally helps support the function of nerve cells. Glioblastomas are difficult to treat, and long-term survival rates are poor.
Glioblastoma cells depend on the body’s blood supply to give them oxygen and nutrients needed to grow. The cancer cells constantly send signaling molecules to communicate with vascular endothelial cells, the cells that line the insides of blood vessels. Vascular endothelial cells, in turn, release signaling molecules to communicate with glioblastoma cells, which are also thought to help the cancer cells grow.
“By targeting the crosstalk between glioblastoma and vascular endothelial cells, we can develop treatments that prevent the tumor from adapting and surviving,” Harley Kornblum, MD, PhD, a co-author of the study and professor at the University of California Los Angeles, said in a university news story. “This could also improve the effectiveness of treatments, especially radiation, making them more successful in tackling this aggressive cancer.”
Honing in on signaling molecule
Through a battery of experiments in mice and tests using human cancer cells, the researchers demonstrated that endocan, a signaling molecule released by vascular endothelial cells, is heavily involved in glioblastoma growth.
“We demonstrated that the absence of Endocan has a dramatic effect on both [glioblastoma] cells and tumor-associated vasculature, suggesting that this protein might be one of the master regulators of [glioblastoma cell and vascular endothelial cell] crosstalk,” the researchers wrote.
They showed that endocan released by blood vessel cells prompts glioblastoma cells to grow and move, a discovery that sheds light on how the tumor establishes itself in three-dimensional space. Also, when this signaling molecule is absent, glioblastoma tumors aren’t able to establish the network of blood vessels that they rely on to grow.
“Solving how tumors organize themselves is an important challenge,” Kornblum said. “While surgery can remove much of the tumor core, the infiltrative edge often remains following removal, leading to recurrence. Our research suggests endocan is a key player in this process, orchestrating both tumor cell behavior and the development of blood vessels that sustain tumor growth.”
Data also suggested that endocan signaling helps glioblastoma cells to resist radiation therapy, a mainstay type of glioma treatment.
In further experiments, the researchers found that the endocan signaling molecule binds to a receptor protein on glioblastoma cells called PDGFRA. This leads to heightened activity of cMyc, a protein that’s known to play a vital role in the growth of many cancers but has been difficult to target with drugs.
The data suggest that it might be possible to reduce cMyc activity indirectly by modulating Endocan and/or PDGFRA signaling, paving the way for possible new treatment strategies. “Inhibiting the endocan-PDGFRA axis may provide an indirect way to disrupt cMyc’s role in glioblastoma,” Kornblum said.
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