Scary! Pressure Will Accelerate The Occurrence of Malignant Pancreatic Cancer!

In a recent study published in the journal Cancer Cell, researchers from Columbia University Medical Center found that stress may accelerate the development of pancreatic cancer by stimulating the release of “fighting or running away” hormones, β-blockers that inhibit these hormones can effectively increase the survival of cancer-bearing mouse models. In addition, researchers analyzing patients with malignant pancreatic cancer found that patients taking selective β-blockers survived two-thirds more than the former, compared with patients who did not ingest selective β-blockers.

 

Recent studies have shown that emotional and psychological stress play a key role in the development of oncogenic tumors that are thought to occur through the sympathetic nervous system, which releases specific hormones that provide the body with an energy which promotes the body respond to a perceived danger. Timothy C. Wang, MD, said some biologists do not agree with this view because stress is hard to measure in general, and other researchers want to know how stress is linked to some of the body’s biological processes. These biological processes include DNA mutations and the growth of cancer cells in certain organs.

 

Graphical abstract

 

Pressure can promote the pre-cancerous proliferation of the pancreas

 

In the current study, researchers wanted to clarify the link between stress and early pancreatic cancer. They studied mice with a genetic predisposition to abnormal proliferation of pancreatic cells. They first placed the mice in a stressful environment, while control mice were placed in normal conditions and after 14 weeks, 38% of the mice in stressful conditions developed pancreatic lesions of the tumor which were the precursors of pancreatic cancer, whereas the control mice did not appear any damage.

 

As we all know, the researcher Wang said, the body needs a single DNA mutation to open the path of cancer, but our research found that stress seems could drive cancer, too.

 

Stress can act through the pancreas nerves

 

Later on in mice, the researchers found that stress can increase the release of hormones called catecholamines in the bloodstream. Catecholamines in the pancreas can drive the production of ADRB2 and NGF that stimulate the growth of peripheral nerves of the tumor, which in turn induce tumor development and make more catecholamines, allowing the process to cycle continuously. These findings suggest that catecholamines drive a feedforward loop, whereby upregulation of neurotrophins increases sympathetic innervation and local norepinephrine accumulation. In other words, pressure can set a feed-forward loop between nerves and cancer cells to promote tumorigenesis.

 

Nonselective β-blockers could improve the survival of patients with pancreatic cancer

 

Chronic neuropsychological stress promotes Kras-induced pancreatic tumorigenesis, ADRB2 blockade significantly increases overall survival in KPC mice (LSL-Kras+/LSL-G12D; LSL-Trp53+/R172H; Pdx1-Cre (KPC) model, which develops early PanIN lesions at 7–9 weeks of age, advanced PanIN lesions at 13–15 weeks, and PDAC by 17–19 weeks). Then the researchers investigated the underlying mechanisms by which adrenergic signaling stimulates PDAC development, and found that Catecholamines could promote acinar to ductal metaplasia and drive proliferation. Adrenergic signaling increases neurotrophin secretion and promotes PDAC development through tumor-associated axonogenesis. They found that blockade of the NGF/Trk pathway could inhibit proliferation and innervation, and increases the overall survival of KPC mice. The researchers designed experiments and analyzed previous data to clarify the relevance of ADRB2 signaling and nerve-cancer interactions in human PDAC and whether there was a correlation between ADRB2 blockade and clinical outcome in PDAC, they found nonselective B-blocker treatment increases overall survival IN surgically resected PDAC patients

 

Using chemotherapy and non-selective β-blocker therapy to study different mouse models of pancreatic cancer, the investigators noted that the survival of cancer-bearing mice was significantly longer than those mice treated with chemotherapy alone. In the article, researchers analyzed the survival of 631 cancer patients between 2002 and 2013 who underwent surgical treatment of malignant pancreatic cancer and nonselective β-blockers after surgery. Their mean survival time was 40 months which was prolonged by two-thirds as compared with patients treated with either selective beta blockers or other types of beta blockers.

 

The researchers point out that the recommendation to use β-blockers to treat patients with pancreatic cancer may not be premature, and more clinical trials are needed to confirm later in life, but β-blockers do serve as part of the treatment for pancreatic cancer.

 

 

Could decompression inhibit or slow down the occurrence of pancreatic cancer?

 

At last, researcher Wang said that many studies and abundant evidence show that maintaining optimism is good for the health of the body and can help patients recover from disease. Could optimism and positive attitude change the prognosis of patients with malignant pancreatic cancer? Probably not. However, maintaining such a mentality certainly will not do any harm, and it may be part of the patient’s overall treatment to help improve the patient’s course of treatment and prognosis.

 

 

 

Reference

Renz BW, Takahashi R, Tanaka T, et al. β2 Adrenergic-Neurotrophin Feedforward Loop Promotes Pancreatic CancerCancer Cell. 2018 Jan 8;33(1):75-90.e7. doi: 10.1016/j.ccell.2017.11.007