Targeting The Spread of Pancreatic Cancer

Garvan Institute of Medical Research has published an article regarding the key to targeting the spread of pancreatic cancer. Pancreatic tumors consist of cancer cells that are interwoven with blood vessels and matrix fibers.

A team of international researchers has revealed how aggressive pancreatic cancer cells change their environment to enable easy passage to other parts of the body. This metastasis is the main cause of pancreatic cancer-related deaths.

Some pancreatic tumors produce a molecule called perlecan to remodel the environment around them that also helps the cancer cells to spread more easily to other parts of the body and protects them against chemotherapy. Researchers have shown through a mouse model that lowering the levels of perlecan revealed a reduction in the spread of pancreatic cancer and also improved the response to chemotherapy.

Associate Professor Paul Timpson, Head of the Invasion and Metastasis Laboratory and Dr. Thomas Cox, Leader of the Matrix and Metastasis Group at the Garvan Institute of Medical Research led the research that may provide a promising new path to more effective treatment options for individuals with pancreatic and other cancers. These findings are published in the journal Nature Communications.

Because pancreatic cancer is so aggressive, the tumor is often inoperable by the time most cases are diagnosed. This is one of the most lethal forms of cancer with a 5-year survival rate of 9% in Australia. It often shows no obvious signs or symptoms in its early stage, so it has begun to spread outside the pancreases by the time it is diagnosed.

The team investigated why some pancreatic cancers spread while others appeared to stay in one place. They compared the rise around tumor cells in metastatic and non-metastatic pancreatic cancers. The tissue is known as the matrix which acts like a glue that holds different cells in an organ or in a tumor together. Using these models they extracted fibroblasts from spreading and non-spreading pancreatic tumors. By mixing different fibroblasts with the cancer cells, they found cancer cells from a non-spreading tumor began to spread when mixed with fibroblasts from a spreading tumor. This suggests that some pancreatic cancer cells can educate the fibroblasts in and around the tumor and let the fibroblasts remodel the matrix to interact with other, less aggressive cancer cells that support the cancer cells’ ability to spread.

In a growing tumor, a few bad apples can help to increase the spread of other, less aggressive cancer cells. They took a closer look at the fibroblasts and how to stop the cells from remodeling the matrix around them. They discovered an unknown set of matrix molecules that aggressive cells use to shape the tissue around them to protect them from chemotherapy and enable easier escape around the body. They believe there would be an important benefit in targeting the fibroblasts of a tumor in combination with targeting the cancer cells themselves with chemotherapy. Specifically targeting the aggressive fibroblasts harboring precise genetic changes could make them more susceptible to the currently approved treatments making significant changes how this aggressive cancer is treated.

The environment of tumors is a potentially untapped resource for cancer therapy which they intend to further explore.

Dr Fredda Branyon