In a search for much needed new treatments for pancreatic cancer - a deadly and aggressive disease with a poor survival rate - scientists are looking for clues at the molecular level. Now, a new study finds that a small molecule called MIR506 appears to play an important role in the fate of pancreatic cancer cells, and may offer a way to stop their growth and ability to spread.
The study - published in the journal Autophagy - is the work of a team led by Wei Zhang, a professor in cancer at Wake Forest Baptist Medical Center in Winston-Salem, NC.
Pancreatic cancer is a disease that starts when abnormal cells develop in the pancreas - a fish-shaped organ behind the stomach that makes hormones and enzymes. As the cells grow out of control, they form a tumor that grows and spreads.
The most common type of pancreatic cancer is pancreatic ductal adenocarcinoma (PDAC).
PDAC usually starts in the ducts of the pancreas - tiny tubes through which digestive enzymes secreted by the organ's exocrine cells begin their journey to the intestines.
Pancreatic cancer - most frequently in the form of PDAC - is the most aggressive and deadly of all cancers. Unfortunately, there are few effective treatments aside from surgery, and even that option is not available to many patients, note the study authors.
Although it only accounts for 3 percent of all cancers, pancreatic cancer accounts for around 7 percent of all cancer deaths in the United States, where it is estimated that 53,670 people will be diagnosed with the disease and 43,090 will die of it in 2017.
Study explores role of small molecule in cancer cell death
The new study concerns a molecule that helps to control a complex cell process called autophagy - a term that comes from the Greek for "eating of self."
Autophagy helps cells to "balance sources of energy" at critical times - such as during development or when nutrients are scarce. It plays a key role in cellular housekeeping, helping to clear out unwanted elements such as misfolded proteins, damaged components, and pathogens.
Although generally thought of as a mechanism for cell survival, autophagy can also be involved in programmed cell death, and it is in this capacity that the new study looks at the molecular mechanism of autophagy in pancreatic cancer cells.
Previous studies had already revealed that a small molecule called MIR506 - a microRNA produced in the human body - behaves as a tumor suppressor in many types of cancer and improves the effect of chemotherapy in ovarian cancer. It exerts these effects through several different signaling pathways.
Prof. Zhang and colleagues decided to investigate the role of MIR506 in pancreatic cancer; they had a hunch that it might play a role in autophagy. They note in their study report:
"In this study, we hypothesized that MIR506 exerted a tumor suppression function in PDAC by inducing autophagy-related cell death."
MIR506 leads to "autophagy-related cell death"
For their investigation, the team studied mice implanted with tumor tissue removed from pancreatic cancer patients during surgery.
When they measured the levels of MIR506 in the mice, the team noticed that they were lower in pancreatic tumors than in a normal pancreas.
Further tests showed that adding MIR506 to experimental tumor cells stopped cancer cell growth and blocked the cell function that causes them to metastasize - the process by which cells migrate from the primary tumor to set up secondary tumors in neighboring tissue and other parts of the body.
Finally, the researchers observed that MIR506 appeared to be exerting this effect through autophagy. "MIR506 triggered autophagic flux in PDAC cells," they note. The result was "autophagy-related cell death through direct targeting" of a signal pathway called the STAT3-BCL2-BECN1 axis.
The authors say that their study adds to knowledge about how MIR506 works as a tumor suppressor - it appears that the molecule also exerts an effect through autophagy-related cell death. The findings suggest a strategy for using MIR506 to target STAT3 in the treatment of PDAC, they conclude.
"The potential therapeutic value of this finding is important because we could deliver MIR506 directly to pancreatic cancer cells using technologies like nanoparticles and exosomes. Hopefully, this will provide us with a new way to fight this deadly form of cancer."
Prof. Wei Zhang