Researchers are attempting to discover new effective therapies for cancer. Well, scientists from University of Texas M. D. Anderson Cancer Center claim that chronic stress may activate a sequence of molecular events that shields breakaway ovarian cancer cells from obliteration.
In preclinical research, the team discovered that heightened levels of the fight-or-flight stress hormones, epinephrine and norepinephrine apparently allow more malignant cells to securely leave the primary tumor, an essential step in metastasis and cancer progression. It was also seen that ovarian cancer patients appear to face earlier mortality when a vital protein triggered by the hormones is there at elevated levels in their tumors.
“When normal cells become detached from neighboring cells or from the supportive scaffolding known as the extracellular matrix, they die from anoikis, a form of programmed cell death. Cancer cells find a way to bypass anoikis, so they survive as individual cells circulating in the blood or in ascites, fluid that accumulates in the abdomen of ovarian cancer patients. Restoring cancer cells’ vulnerability to anoikis would open a new avenue for suppressing tumor growth and metastasis,” commented, first author Anil Sood, M.D., professor in M. D. Anderson’s Departments of Gynecologic Oncology and Cancer Biology.
Two potential approaches, straightaway silencing a vital protein or utilizing beta blockers to anticipate its activation, supposedly worked in cell culture and mouse models, making them applicants for human use. The team exhibited that augments in epinephrine, also called adrenaline and norepinephrine decreased the amount of ovarian cancer cells destroyed by anoikis by triggering focal adhesion kinase (FAK). This protein is apparently known to endorse tumor survival and to shield against anoikis. The researchers formerly exhibited that FAK is said to be there a lot in ovarian cancer cells.
Lab experiments exhibited that resistance to cell death by anoikis starts when one of the hormones binds with the ß2-adrenergic receptor (ADRB2), which triggers FAK by means of other intermediate proteins. In a mouse model of human ovarian cancer, mice subject to restraint stress appeared to have lesser tumors with fewer nodules and larger cell death when treated with siRNA to repress FAK. Treatment with the beta blocker propranolol apparently encompassed a comparable effect.
The researchers investigated roughly 80 cases of invasive epithelial ovarian cancer to evaluate the function of stress-induced FAK activity. They discovered augmented FAK expression in roughly 67 percent of patients and heightened levels of phosphorylated FAK in around 50 percent.
Patients with elevated levels of either measure had significantly decreased by and large survival by more than three years. Approximately 65 percent of those with low FAK expression survived at least three years as opposed to those with 30 percent with high expression. For activated FAK, the difference was said to be around 65 percent as against 5 percent.
By means of depression as a pointer of stress, the scientists discovered that major depression was said to be linked to higher levels of activated FAK and augmented levels of norepinephrine in the tumors. Major depression was seemingly defined as a score more than 16 on the Center for Epidemiological Studies Depression [CESD] scale for this research.
The research was published in the Journal of Clinical Investigation.