神经对前列腺癌的扩散起关键作用

Researchers at Albert Einstein College of Medicine of Yeshiva University have found that nerves play a critical role in both the development and spread of prostate tumors. Their findings, using both a mouse model and human prostate tissue, may lead to new ways to predict the aggressiveness of prostate cancer and to novel therapies for preventing and treating the disease. The study published online today in the July 12 edition of Science. Prostate cancer is second to skin cancer as the most common cancer in men. The National Cancer Institute estimates that 238,590 new cases of prostate cancer will be diagnosed in 2013, and 29,720 men will die from the disease.

 

The study was led by stem-cell expert Paul Frenette, M.D., professor of medicine and of cell biology and director of the Ruth L. and David S. Gottesman Institute for Stem Cell and Regenerative Medicine Research at Einstein. In earlier research, Dr. Frenette and colleagues had discovered that the sympathetic（交感神经的） nervous system regulates hematopoeitic stem cell niches³ -- the sites in the bone marrow⁴ where red blood cells are formed.

 

Nerves are commonly found around tumors, but their role in the growth and progression of cancer has not been clear. "Since there might be similarities between the hematopoeitic stem cell niche² and the stem cell niches found in cancer, we thought that sympathetic nerves might also have a role in tumor¹ development," said Dr. Frenette. "It turns out that in prostate cancer, not only are sympathetic nerves involved, but so too are parasympathetic nerves（副交感神经）."

 

The body's autonomic nervous system (governing functions that we don't consciously control, such as heart rate) is divided into two branches. The sympathetic nervous system, or SNS, modulates⁵ the body's "fight or flight response" by, for example, revving⁶ up the heart rate and constricting⁷ blood vessels⁸. The parasympathetic nervous system, or PNS, generally acts in opposition⁹ to the SNS to keep bodily functions in balance.

 

The researchers discovered the role of nerves in prostate cancer by first injecting human prostate cancer cells into mice and then systematically¹⁰ disabling various parts of the SNS and PNS and observing how the cells fared. A control group of mice were administered the cancer cells but underwent no further interventions¹¹.

 

The study found that the autonomic nervous system's two branches have complementary functions in the development and spread of prostate cancer. The SNS helps initiate¹² the early phases of the disease, while the PNS is involved in the later stages when the cancer spreads.

 

More specifically, the researchers found that the SNS promotes tumor growth by producing the neurotransmitter norepinephrine, which then binds¹³ to and stimulates¹⁴ two types of adrenergic receptors (beta-2 and beta-3) on the surface of the stromal cells in the tumor (adrenergic receptors are targeted by adrenaline and noradrenaline, also known respectively as epinephrine and norepinephrine). "This is consistent with recent epidemiological studies showing that the use of beta-blockers, which lower blood pressure by blocking beta-adrenergic receptors, is associated with improved survival of prostate cancer patients," said Dr. Frenette.

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