New research from the University of Washington in St. Louis (USA) shows that glioblastoma has an internal clock and synchronizes its daily rhythms to adapt to the rhythms of your guest and take advantage of them; In this way, brain tumors grow in response to the daily release of steroid hormones by guestlike cortisol.
In depth
Washington University scientists They discovered that the blockade of circadian signals drastically slowed the growth of glioblastoma and the progression of the disease. This process worked both in plaque cells and in animals with tumors, according to the study published in ‘Cancer Cell’.
“The glioblastoma is governed by the hormones released by the same central host clock that establishes the regular daily rhythms of the body“, develops Erik D. HerzogProfessor of Biology in Arts and Sciences and main author of the study. “Blocking the daily increase in glucocorticoid signaling discourages the circadian rhythms of the guest of the guest and drastically slows down the progression of the disease in tumor carriers mice.”
“Our previous investigations helped us see a pattern,” notes Dr. María F. González-Aponte, first author of the study. “Whether we were analyzing clinical data as if we were analyzing cells derived from patients or mice With model glioblastoma tumors, chemotherapy treatment always worked better around normal vigil schedule. That is what led us to think that these tumors knew the time of day abroad“
The findings are important in part because they affect the way glioblastoma tumors respond to a drug called dexamethasone (Dex), a synthetic steroid that is commonly administered to patients with glioblastoma to reduce cerebral edema after radiotherapy and surgery. This study discovers that managing Dex in the morning promotes tumor growth in mice, while administering it at night suppresses growth.
More details
“For many years, the use of Dex for glioblastoma has been controversial due to studies that show promoting effects or growth suppressants,” González-Aponte points out. “We knew that glioblastoma has daily rhythms, so we immediately ask ours“He says.
Every day, just before a person or an animal wakes up (in response to light and other environmental signals), the brain sends a signal to the adrenal glands to release a wave of steroid hormones called glucocorticoids. These hormones participate in the known fight or flight response, but also regulate a variety of more essential biological processes, such as metabolism and immunity.
“Under normal conditions, glucocorticoid levels drastically increase every day before waking up,” he says González-Aponte. She and Herzog raised the hypothesis that glioblastoma responds to this reliable daily discharge of glucocorticoids to synchronize their clock with that of their host. To try this idea, González-Aponte First it set out to see if he could alter the sense of time of a tumor restoring the daily rhythms of his host.
Placed mice with tumors in cages that could be illuminated or darkened with a timer. When changing the moment he turned on the lights, González-Aponte convinced the mice to adopt an inverted schedule. He realized that he was working when observing when every day the mice began to run on their wheels. “The mice run more on their wheels during the night than during the day,” González-Aponte recalls. “When we invest the light and dark schedule, it is basically like flying from San Luis to India. We are forcing them to resolve“
As the mice adapted to their new inverted schedules, scientists monitored cancer cells in the tumors of their brains to detect changes. They used a novel method to obtain images of the expression of the clock gene in the cancer cells of the mice that behaved freely, collecting data every minute for several continuous days. The scientists observed that Two clock genes in cancer cells, BMAL1 and PER2, changed their schedules as the mice changed their schedules.
To take into account
“What we found was that BMAL1 and PER2 do the same as the mouse on the wheel. That is, cancer cells are resyling their daily rhythms as the mouse resolves its locomotive activity“, details González-Aponte. Similarly, the tumors remained synchronized with the guest in conditions in which the mice woke up and slept according to their own circadian cycles in the absence of any environmental synchronization signal.
González-Aponte and Herzog They suspected That if glioblastoma has its own reliable circadian rhythms, then its response to DEX (a synthetic glucocorticoid hormone) could vary according to the time of the day the DEX was administered.
To check it, they leaned on An additional set of experiments that demonstrated that glucocorticoids promote or inhibit the growth of glioblastoma cells According to the time of day. In mice with glioblastoma brain tumors, scientists discovered that The tumor size increased significantly if dex was administered in the morning, compared to applications at night or control.
These findings, made in mice, have implications for the use of glucocorticoids such as DEX in clinical practice, says González-Aponte. More research is needed to determine If there are times of the day in which DEX can be used to reduce cerebral edema without promoting glioblastoma growth.
#investigation #shows #brain #tumors #kidnap #circadian #clock #grow
