Cancer Cells Exploit Neuron-Glia Interactions to Promote Brain Metastasis

One insidious thing breast cancer cells do is their method of metastasizing to the brain. By sending out vesicles filled with microRNA, these cells manipulate the brain's nutrient environment, creating favorable conditions for metastasis.

The Challenge of Brain Metastasis

Breast cancer is notorious for metastasizing, with about 10 to 16 percent of breast cancer patients experiencing brain metastasis. Although strides have been made in treatments such as chemotherapy, the brain continues to be a safe haven for these cancer cells. To survive and thrive in this harsh environment, cancer cells have developed clever tactics.

"The brain is not the easiest place for cells to grow," says Marsha Rosner, a cancer biologist at the University of Chicago. "They need some help."

Implications for Treatment

This research provides a key missing link in the process of how cancer spreads to the brain. "Likely metabolism plays a key role in metastasis as a whole," Rosner writes. According to Wang's research, this metabolic tampering is not limited to breast cancer alone, which could lead to some understanding of other cancers that metastasize to the brain.

This discovery highlights the potential for new therapeutic targets. By disrupting the cancer cells' ability to manipulate brain metabolism, it may be possible to prevent brain metastases and improve outcomes for patients facing this difficult challenge.

Manipulating Brain Cells for Survival

Scientists at the University of California, San Diego, led by Shizhen Emily Wang, have recently discovered that breast cancer cells release extracellular vesicles (EVs) containing microRNAs that allow them to invade the brain, according to a new study in Nature Communications. This research uncovers a very intricate process of how cancers manipulate the brain cells to create a more favorable environment for their proliferation.

The Role of MicroRNA in Metastasis

MicroRNAs are known to regulate gene expression and are essential for the process, however, the exact role of these small molecules in metastasis has been a great mystery. "Cancer cells don't go to the trouble of making and releasing microRNAs for nothing," Wang said.

They studied the breast cancer cells that are known to metastasize or spread to the brain. When they analyzed the microRNA content of EVs secreted by these cells, they identified miR-199b as a key player. This particular microRNA targets genes that are involved in the metabolic interplay between neurons and glial cells in the brain.

How Cancer Alters Brain Metabolism

Glutamate is released by the neurons and taken up by glial cells, where it is converted back into glutamine, and this cycle is necessary for the brain to function. Mir-199b throws off this balance because it alters the levels of three important genes (slc1a2, slc38a2, and slc16a7) needed for this recycling. MiR-199b tinkers with the brain's nutrient exchange system and creates excess nutrients such as glutamine and lactate, which are then stolen by the cancer cells and used as energy for growth.

The researchers observed that when brain cells were exposed to EVs with high levels of miR-199b, their consumption of metabolites like glutamate and lactate decreased, effectively leaving more nutrients available for the invading cancer cells. Mice injected with these vesicles exhibited an increase in brain metastases, even though their primary breast tumors remained relatively unchanged.

Implications for Treatment

This research provides a key missing link in the process of how cancer spreads to the brain. "Likely metabolism plays a key role in metastasis as a whole," Rosner writes. According to Wang's research, this metabolic tampering is not limited to breast cancer alone, which could lead to some understanding of other cancers that metastasize to the brain.

This discovery highlights the potential for new therapeutic targets. By disrupting the cancer cells' ability to manipulate brain metabolism, it may be possible to prevent brain metastases and improve outcomes for patients facing this difficult challenge.

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