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Perlecan Enables Pancreatic Cancer to Spread, Resist Chemo

Fibroblast cells.

Researchers have determined that some pancreatic tumors can remodel their environments when their fibroblasts, cells that comprise connective tissue, produce high levels of a molecule called perlecan, enabling cancer cells to spread throughout the body more easily.

With a five-year survival rate of only 7% and a median survival of less than one year, pancreatic cancer is one of the most aggressive forms of cancer and frequently remains undetected until after it has spread. There is a need to develop alternative treatment options that can improve the efficacy of chemotherapy and reduce tumor progression.

Researchers at the Garvan Institute of Medical Research in Sydney, Australia, are focusing their efforts not only on cancer cells themselves, but also on the environment surrounding tumors. Led by first author Claire Vennin, PhD, a Research Officer at the Garvan Institute of Medical Research and a postdoctoral fellow at The Netherlands Cancer Institute in Amsterdam, they have determined that pancreatic tumors whose fibroblasts produce higher levels of perlecan, a proteoglycan molecule, can change the tissue that surrounds the tumor and holds its cells together.

Dr. Vennin and colleagues extracted fibroblasts from both metastatic and nonmetastatic tumors in mice and combined them with cancer cells. When combined with fibroblasts from metastatic tumors, the cancer cells from the nonmetastatic tumors also began to spread, suggesting that fibroblasts can remodel the tissue and enable the cancer cells to spread more easily. The researchers discovered that the fibroblasts from metastatic tumors produced high levels of perlecan. Reducing perlecan levels in the tumors inhibited the spread of cancer cells and caused the tumors to respond more effectively to chemotherapy.

"We believe that there would be important benefit in targeting the fibroblasts of a tumor in combination with targeting the cancer cells themselves with chemotherapy," conclude Dr. Vennin and colleagues in their study, now published in Nature Communications. "If we can specifically target the aggressive fibroblasts in patients harboring precise genetic changes, we can make them more susceptible to our currently approved treatments, which would significantly change how we treat this aggressive cancer."

For More Information

Vennin C, Merlenec P, Rouet R, et al (2019). CAF hierarchy driven by pancreatic cancer cell p53-status creates a pro-metastatic and chemoresistant environment via perlecan. Nat Commun. [Epub ahead of print] DOI: 10.1038/s41467-019-10968-6

‚ÄčImage credit: Heiti Paves. Licensed under CC BY-SA 3.0

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