An international team of researchers has revealed how aggressive pancreatic cancer cells change their environment to enable easy passage to other parts of the body (metastasis) - the main cause of pancreatic cancer-related death. The researchers discovered that some pancreatic tumors produce more of a molecule called “perlecan” to remodel the environment around them, which helps cancer cells spread more easily to other parts of the body, and also protects them against chemotherapy. In a mouse model, the researchers showed that lowering the levels of perlecan reduced the spread of pancreatic cancer and improved response to chemotherapy. Led by Associate Professor Paul Timpson, PhD, Head of the Invasion and Metastasis Laboratory, and Thomas Cox, PhD, Leader of the Matrix and Metastasis Group, both at the Garvan Institute of Medical Research in Australia, the research may provide a promising new path to more effective treatment options for individuals with pancreatic and other cancers. The findings were published online on August 12, 2019 in Nature Communications. The open-access article is titled “CAF Hierarchy Driven by Pancreatic Cancer Cell p53-Status Creates a Pro-Metastatic and Chemoresistant Environment via Perlecan.”"Pancreatic cancer is very aggressive, and, by the time most cases are diagnosed, the tumor is often inoperable," says Associate Professor Timpson. "What we've discovered in this study is a two-pronged approach for treating pancreatic cancer that we believe will improve the efficiency of chemotherapy and may help reduce tumor progression and spread." Pancreatic cancer is one of the most lethal forms of cancer, with a five-year survival of ~9% in Australia.
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