Researchers Target How Pancreatic Cancer Cells Spread

Molecular partnership may generate much-needed new treatments for the disease.

A discovery on molecular interaction may lead to much-needed new treatments for pancreatic cancer.

Scientists at the Johns Hopkins Kimmel Cancer Center have identified a molecular partnership in pancreatic cancer cells that may explain how the disease spreads, according to recent research. The findings shed light on new targets to treat pancreatic cancer, a disease that strikes nearly 50,000 people in the United States each year and has only a 5% survival rate 5 years after diagnosis.

One of the molecular partners found in the study is annexin A2, a protein that scientists contend was already linked to poor survival rates in pancreatic cancers. In a report published in the August 4, 2015 issue of Science Signaling, researchers showed that annexin A2 helps chaperone a protein called Sema3D out of pancreatic cancer cells. Once outside the cells, Sema3D joins with another molecule to fuel cancer spread.

In experiments conducted in mice, researchers calculated a seventyfold drop in the amount of Sema3D secreted from mouse pancreatic cancer cells in animals that lacked annexin A2. Of 23 mice experimented on, none of the annexin-free animals developed visible metastatic tumors. Contrarily, 16 of 17 mice that produced annexin A2 in their cells developed metastatic tumors in the liver, lungs, or abdomen.

A second group of experiments using human tissue from patients with pancreatic ductal adenocarcinoma revealed a link between the abundance of Sema3D in those tissues and the progression of metastatic pancreatic cancer. The team of scientists report that Sema3D was abundant in the main tumor tissue of just 3 out of 13 patients who died after minimal cancer metastasized.

However, it was abundant in the main tumors of 14 of 22 patients who died with widely spreading cancer. Additionally, it was abundant in the metastatic tumors of 17 of 23 patients.

According to the research, the presence of Sema3D seems also to be connected with the recurrence of pancreatic cancer in patients whose primary tumors were surgically removed as Sema3D was abundant in the primary tumors of approximately 75% who lived free of cancer for less than 1 year after their surgery.

With the addition of this latest research, scientists are pursuing 3 possible therapeutic targets to stop pancreatic cancer spread driven by annexin A2 and Sema3D.

“We are planning clinical trials with a recently developed vaccine to target annexin A2,” said Lei Zheng, MD, PhD, an associate professor of oncology and surgery at the Johns Hopkins University School of Medicine. “But at the same time, we are also developing a therapeutic antibody targeting annexin A2, and we are looking for a small molecule that would inhibit Sema3D.”