Pancreatic cancer is deadly all by itself, but like so many cancers it can metastasize, becoming even deadlier. The mechanism by which the cancer spreads is not well understood, but a group of Johns Hopkins researchers recently made progress. A team at the Kimmel Cancer Center identified a molecular partnership, a sort of deadly teamwork between two proteins that is implicated in the metastasis.
The first protein, annexin A2, is involved in a number of cellular processes within the body, including cell motility and what is called exocytosis—the movement of proteins from within cell walls to outside them. In regard to pancreatic cancer, annexin A2 seems to help the second protein in the partnership, semaphorin 3D, exit pancreatic cancer cells.
Once Sema3D is outside the malignant cells, the real mischief begins. Pancreatic cancer is neurotropic, meaning it tends to invade nerve cells. Sema3D may help the cancer do this by tracking and surrounding nerves in order to put the cancer cells on a neural highway, so to speak, facilitating their spread. The presence of Sema3D has also been implicated in the recurrence of cancer after primary pancreatic tumors have been surgically removed.
Exactly how annexin A2 encourages pancreatic cancer cells to release Sema3D has not been determined. It may act as a sort of bodyguard, sheltering and guiding the protein as it makes its way toward an exit point at the cell's surface.
Two of the paper's authors, Lei Zheng and Elizabeth M. Jaffee, both oncologists in the School of Medicine, hold a patent on annexin A2 as a target for cancer therapy. They plan to conduct clinical trials on a vaccine targeting the protein, and they're also hunting for a molecule that might inhibit Sema3D.