Author: Bolysbek Dana
Editor: Merentsova Anastasia
Pancreatic cancer is of particular concern. At the moment, the disease is diagnosed only in the late stages, when it is difficult to treat. Therefore, the mortality rate from it is high. About 95 percent of all pancreatic cancers are so-called adenocarcinomas. In the past, there were attempts to find out the genetic differences in their types, but it turned out that all adenocarcinomas of the pancreas carry a similar set of mutations. Now the team of scientists has taken a different approach. They based their studies on the methylation patterns of purified tumor cells. From patient tissue samples, they first isolated pure cancer cells from a complex tumor cell mixture, which contains a large number of connective tissue, blood vessels and immune cells. The researchers then searched the genome of the purified tumor cells for differences in methylation patterns. So they were able to identify two completely different subtypes of adenocarcinomas, which differ in carcinogenesis and aggressiveness. One of the two subtypes is much more aggressive and actually develops directly from the ductal cells lining the pancreatic duct system, while less aggressive tumors develop from the glandular cells.
Also, upon closer inspection of methylation patterns, the researchers found that the more aggressive subtypes had fewer methyl groups. They contained sequences of so-called endogenous retroviruses, the remains of viruses that have remained in the human genome during evolution. In healthy people, they have methyl groups, and thus are muffled. However, in this subtype, they become active again after the removal of methyl groups and form double-stranded RNA strands.
This type of RNA molecule is not usually found in a healthy body and therefore can be a signal for the immune system to invade a virus. As a result, the interferon system is activated and tries to fight "viruses". As a result, inflammation occurs in the immediate vicinity of the tumor. Simulating a viral infection in genetically modified tumor cells is called viral mimicry. In a tumor, viral mimicry promotes inflammatory responses that further stimulate cancer growth and, in addition, probably stimulate metastasis, that is, the spread of the tumor.
The researchers found viral mimicry only in the ductal subtype, and in trace amounts also in healthy ductal cells, but not in healthy pancreatic glandular cells or pancreatic cancer cells of a less aggressive subtype. This explains why pancreatic tumors that develop from cells of the pancreatic ducts, which account for about one third of the tumors examined, are especially aggressive.
This study opens up more targeted treatments for pancreatic cancer. By blocking the signaling pathways of interferon at various sites, the scientists were able to significantly slow down cancer growth in mice transplanted with human pancreatic cancer cells. However, the regulation of these signals is still very difficult.
Source: https://medicalxpress.com/news/2020-10-pancreatic-cancer-subtypes-aggressiveness.html
