Researchers identify ANO6 as a potential target against pancreatic cancer — News-Medical

Researchers at Fox Chase Cancer Center found that blocking the protein anoctamin 6, or ANO6, may slow the growth of pancreatic tumors and reduce suppression of the immune response in preclinical models. News-Medical reports on the results of the study, published in the journal Nature Cancer.

Fibroblasts supply the tumor with lipids The study concerned pancreatic ductal adenocarcinoma, the most common type of this cancer. Such tumors are surrounded by dense connective tissue and have relatively few functional blood vessels. The scientists focused on cancer-associated fibroblasts, cells that make up a significant portion of the tissue surrounding the tumor.

According to the authors, these fibroblasts obtain cholesterol from the bloodstream and transfer it to nearby cancer cells through a process called trogocytosis. During this process, tumor cells take small fragments of fibroblast membranes, along with which they receive cholesterol and other lipids needed for survival and growth.

ANO6 helps prepare the fibroblast membrane for this transfer. In laboratory and animal models, reducing or eliminating ANO6 weakened these cells' ability to support cancer cell survival. More current news is available on the UA.News Telegram channel Telegram .

Effects on T cells The same mechanism, the researchers concluded, may also affect cytotoxic T lymphocytes, immune cells capable of recognizing and destroying cancer cells. During direct contact with fibroblasts, T cells can also receive fragments of their membranes, including cholesterol.

Its excess in the tumor environment is associated with T-cell exhaustion and reduced effectiveness. In mouse models, blocking ANO6 reduced cholesterol accumulation in T cells that had infiltrated the tumor and improved measures of their activity. Separately, in laboratory experiments, T cells that came into contact with fibroblasts with reduced ANO6 levels destroyed cancer cells more actively.

The authors also tested niclosamide and clofazimine, drugs that suppressed ANO6-dependent activity within the study. In mouse models, treatment with them significantly reduced tumor mass, while niclosamide reduced cholesterol delivery to pancreatic cancer cells. The researchers stressed that trogocytosis is only one of the ways tumor cells obtain lipids, so further research is needed to assess the selective impact of targeting ANO6 as a treatment method.