Sylvie Deborde, PhD

Sylvie Deborde, PhD
Assistant Attending Biologist
Memorial Sloan Kettering Cancer Center

Retinoic acid in Schwann cells involved in pancreatic cancer invasion

Overview

In pancreatic cancer, nerves infiltrate tumors, promote cancer progression, and allow cancer cells to migrate along them in a process known as perineural invasion (PNI). PNI, which also occurs in other cancers, causes pain and is linked to shorter survival, but no treatments have yet been developed to inhibit the nerve-induced cancer progression. This project aims to address that gap by determining how specific cells within nerves called Schwann cells interact with pancreatic cancer cells and promote cancer invasion. Our studies suggest that Schwann cells are activated by a metabolite of vitamin A called retinoic acid, and that amounts of retinoic acid increase in Schwann cells that are grown with pancreatic cancer cells. We have also found that retinoic acid enhances Schwann cells’ ability to move and promote cancer invasion. Though retinoic acid is generally thought to block cancer growth by inducing tumor cell death or conversion to a non-cancerous cell type, we hypothesize that where nerves interact with a tumor, retinoic acid may instead indirectly promote cancer, as it promotes nerve growth and nerves stimulate cancer progression. Understanding the process by which Schwann cells help cancer spread may lead to therapies that block it, which would reduce pain and could improve survival in pancreatic cancer and other cancers that spread
along nerves. In addition, our findings may lead to reconsideration of retinoic acid-based treatment for cancers associated with nerves.