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Pancreatic cancer cells harness normal tissue turnover to build protective barriers

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In the presence of pancreatic cancer, some antibiotics break down systemic proteins into bacteria that result in the formation of a large tissue, a well-known barrier to treatment, new research has found.

Led by researchers from the NYU Grossman School of Medicine, the study focused on the meshwork function of a large protein that supports organs and helps rebuild damaged tissue. Cholesterol triglyceride, a major component, is continuously broken down and replaced to preserve enduranceand as part of the wound healing process.

Previous studies have shown that antibiotics so-called macrophages contribute to a process called desmoplasia, which is caused by abnormal volume and inhibited collagen storage. pancreatic cancer. In this context, macrophages are also known to consume and break down collagen through the action of a protein called mannose receptor (MRC1).

Posted online April 4 in Submissions of the National Academy of Sciences, Current research has found that collagen degradation increases the amount of arginine, an amino acid used by the enzyme nitric oxide synthase (iNOS) to produce a compound called reactive nitrogen species (RNS). This, in turn, leads to neighboring, stellate cells supporting the formation of collagen roots around tumor cells, the study authors said.

“Our results show how pancreatic tumors form macrophages to help build fibrotic barrier,” said lead author Madeleine LaRue, Ph.D. At the time of the study, LaRue was a postgraduate student in the lab of research author Dafna Bar-Sagi, Ph.D., S. Farber Professor of Biochemistry and Molecular Pharmacology and Assistant Dean of Science at NYU Langone Health. “This genetic system can be used to treat cancer changes in the tissues surrounding tumors,” LaRue added.

Pancreatic cancer is the third leading cause of autoimmune death in the United States, with a five-year survival rate of 10%. Pancreatic cancer is difficult to treat in large part due to the large network of fibrotic tissue around the tumors. This network not only blocks access to therapies, but also promotes robust development.

For the present study, experiments showed that macrophages grown in nutrient-dense (culture) dishes, and transformed into cancer cells (M2), disrupted most collagen. than macrophages that attack cancer cells (M1). Further, the team confirmed a series of experiments that M2 macrophages have higher levels of enzymes that cause RNS, such as iNOS.

To confirm these findings in live dances, the group implanted stelate cells that were either “already fed” in conjunction, or kept in an unheated state, in the edges of the study animals with. pancreatic cancer Cells. The team observed a 100 percent increase in the number of intra-tumor collagen fields in tumors derived from cancer cells implanted with stelate. Cells antiviral and collagen.

Importantly, studies have shown for the first time that macrophages are close to the pancreatic cancer cellsNot only do they carry and break down extra collagen as part of the breakdown of proteins that promote unhealthy growth, but they are also altered by damage, such as their energy metabolism. ) regenerates and signals for fibrotic construction.

“Our team has found a way to connect with each other collagen turn to building a drug-resistant environment around pancreatic tumors, ”Bar-Sagi said. cancer “It’s very deadly. We need to understand more about the link between protein breakdown and building a barrier to improve the treatment of this disease.”


Pancreatic cancer cells secrete a signal that damages the body’s immune system against cancerous tumors


Learn more:
Metabolic reprogramming of macrophages associated with proliferation through collagen conversion promotes fibrosis in pancreatic cancer, Submissions of the National College of Science (2022).

Its formation
NYU Langone Health

hintPancreatic cancer cells use a regular tissue transplant to build a protective barrier (2022, April 4) Retrieved 4 April 2022 from https://medicalxpress.com/news/2022-04-pancreatic-cancer- cells-harness-tissue.html

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