Stress hormone may hasten the progression of certain blood cancers

Researchers here have shown that in cell cultures, the stress hormone norepinephrine appears to promote the biochemical signals that stimulate certain tumour cells to grow and spread.

The finding, if verified, may suggest a way of slowing the progression and spread of some cancers enough so that conventional chemotherapeutic treatments would have a better chance to work.

The study also showed that stress hormones may play a completely different role in cancer development than researchers had once thought.

The results appear in the current issue of the journal Brain, Behaviour and Immunity.

“We would not be surprised if we see similar effects of norepinephrine on tumour progression in several different forms of cancer,” explained Eric Yang, first author of the paper and a research scientist with the Institute for Behavioural Medicine Research (IBMR) at Ohio State University.

Yang and colleague Ron Glaser, a professor of molecular virology, immunology and medical genetics, last year showed that the stress hormone norepinephrine was able to increase the production of proteins in cultures of nasopharyngeal carcinoma tumour cells that can foster the aggressive spread of the disease, a process known as metastasis. Glaser is director of the IBMR and a member of the Comprehensive Cancer Center at Ohio State.

In this latest study, the researchers looked at a different type of cancer – multiple myeloma. One of several types of cancers of the blood, multiple myeloma strikes nearly 20,000 Americans each year, killing at least half that many annually. Patients diagnosed with this disease normally survive only three to four years with conventional treatments.

Yang and Glaser focused on three multiple myeloma tumour cell lines, each representing a different stage in the life of the disease, for their experiments. While all three tumour cell lines reacted to the presence of norepinephrine, only one, a cell line known as FLAM-76, responded strongly to the hormone.

The norepinephrine binds to receptors on the surface of the cells, sending a signal to the nucleus to produce a compound known as VEGF — vascular endothelial growth factor – that is key to the formation of new blood vessels, which the tumour must have to grow.

The FLAM-76 cell line was prepared from multiple myeloma tumour cells taken from a patient whose disease had not yet progressed too far from its original site in the bone marrow where blood cells are formed.

“It turns out that FLAM-76 tumour cells more closely represent the earlier stages of the disease when blood vessel formation, a process called angiogenesis, is needed for disease progression,” Yang said.

“The fact that this one cell line, of the three multiple myeloma cell lines studied, closely represents the early stages of the tumour, and that this is where we see the biggest effect, is what makes this work more clinically relevant,” Glaser said.

The researchers believe that blocking these receptors would slow the process of the growth of more blood vessels to the tumour, delaying disease progression and perhaps allowing treatments to be more effective. Widely used “beta-blocker” drugs now prescribed for high blood pressure work by blocking these same particular cell surface receptors, Yang said.

“This approach wouldn’t kill the tumour cells but it would diminish the blood supply to the tumour cells and slow them down, and that could translate into a longer and better quality of life for the patient,” Glaser said.

The researchers and their colleagues are now working with other forms of cancer to test the effects of stress hormones like norepinephrine on their growth.

Glaser added that these kinds of results may change the way scientists are looking at a link between stress and the development and spread of cancer. In the past, he said, the focus was on how stress hormones weakened the immune system, allowing certain tumours to evade the body’s defences.

“Now we have these stress hormones, not only affecting the immune response, but also acting directly on the tumour cells and inducing changes in the molecules made by those same tumour cells,” Glaser said.

“This has important implications for the spread of the tumour and metastasis.”

Elise Donovan, a researcher with the IBMR, and Don Benson, a researcher with Ohio State’s Comprehensive Cancer Centre, also worked on the project. The research was funded in part by the National Cancer Institute.

(Source: Brain, Behaviour and Immunity: Ohio State University: January 2008)