Galectin-1 protein allows brain tumors to evade the immune system

Brain tumors fly under the radar of the body's defense forces by coating their cells with extra amounts of a specific protein, new research has shown. Like a stealth fighter jet, the coating means the cells evade detection by the early warning immune system that should detect and kill them. The stealth approach lets the tumors hide until it is too late for the body to defeat them.

The findings, made in mice and rats, show the key role of a protein called galectin-1 in some of the most dangerous brain tumors, called high-grade malignant gliomas. A research team from the University of Michigan (U-M) Medical School in Ann Arbor made the discovery and has published it in Cancer Research (2014; doi:10.1158/0008-5472.CAN-14-1203).

In a stunning example of scientific serendipity, the team uncovered galectin-1's role by pursuing a chance finding. They had actually been trying to study how the extra production of galectin-1 by tumor cells affects cancer's ability to grow and spread in the brain.

Instead, they found that when they blocked cancer cells from making galectin-1, the tumors were eradicated; they did not grow at all. That's because the first responders of the body's immune system—natural killer or NK cells—spotted the tumor cells almost immediately and killed them.

But when the tumor cells made their usual amounts of galectin-1, the immune cells did not recognize the cancerous cells as dangerous. That meant that the immune system could not trigger the body's second line of defense, the T cells, until the tumors had grown too large for the body to successfully eradicate.

“This is an incredibly novel and exciting development, and shows that in science we must always be open-minded and go where the science takes us, no matter where we thought we wanted to go,” said team leader Pedro Lowenstein, MD, PhD, of U-M Department of Neurosurgery.

“In this case, we found that overexpression of galectin-1 inhibits the innate immune system, and this allows the tumor to grow enough to evade any possible effective T cell response,” he explained. “By the time it's detected, the battle is already lost.”

The NK-evading stealth function of the extra-thick coating of galectin-1 came as a surprise, because glioma researchers everywhere had assumed the extra protein had more to do with the insidious ability of gliomas to invade the brain, and to evade the attacks of T cells.

Gliomas, which make up about 80% of all malignant brain tumors, include anaplastic oligodendrogliomas, anaplastic astrocytomas, and glioblastoma multiforme. More than 24,000 cases of primary malignant brain tumor are diagnosed in the United States each year.

The tiny tendrils of tumor that extend into brain tissue from a glioma are what make them so dangerous. Even when a neurosurgeon removes the bulk of the tumor, small invasive areas escape detection and keep growing, unchecked by the body.

Helping the innate immune system to recognize early stages of cancer growth, and sound the alarm for the body's defense system to act while the remaining cancer is still small enough for them to kill, could potentially help patients
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