Researchers have identified a marker on pancreatic tumor cells that may help identify important tumor-initiating cells. The marker, CD47, is expressed at high levels on both pancreatic neuroendocrine tumor (PNET) cells and pancreatic ductal adenocarcinoma tumor cells from patients. CD47 was found to be expressed on two cell populations-the population thought to be tumor and metastasis initiating, as well as the bulk tumor population.
Geoffrey W. Krampitz, MD, doctoral candidate at the Institute for Stem Cell Biology and Regenerative Medicine at Stanford University School of Medicine and colleagues, also found that a monoclonal antibody blocking CD47 can eliminate both PNET and pancreatic ductal adenocarcinoma in pre-clinical models. Krampitz presented these results at a press conference at the American Association for Cancer Research (AACR) special meeting, "Pancreatic Cancer: Innovations in Research and Treatment", held May 18-21, in New Orleans.
Currently, patients with PNET and pancreatic ductal adenocarcinoma have few therapeutic options and there are also few known targets for drug development known in pancreatic cancer. Targeting CD47 is therefore a potential way to eliminate tumor-initiating cells.
Prognosis for patients with pancreatic cancer remains poor. The 5-year survival rate for patients, which are typically diagnosed with late-stage disease, is only 6%. In the U.S., pancreatic ductal adenocarcinoma (PDAC) is the fourth leading cause of death from cancer.
Analysis of tumor samples from 19 patients with PNET and from 39 patients with pancreatic ductal adenocarcinoma whom had part of their cancer removed by surgery, showed that select cells in each tumor had tumor-initiating characteristics with elevated CD47 marker levels.
Transplanting mice with tumors from either PNET or pancreatic ductal adenocarcinoma patient samples followed by treatment with the anti-CD47 antibody resulted in tumor regression.
CD47 is a transmembrane protein found on a variety of cells. The marker has been found to function in an array of cell processes including proliferation, apoptosis, cell migration, and is known to have a key role in immune and angiogenesis responses. “CD47 is a widely expressed cell surface protein,” said Krampitz during the press conference.
CD47 on the cell surface provides a protective signal for macrophages, a type of circulating immune cell, not to sacrifice these cells. Older, damaged cells that need to be removed by the immune system lose their CD47 marker and are consumed by these immune cells.
CD47 has also been found to be over-expressed on many other tumor types, both solid and hematological cancers. “Most cancer cells express CD47 to evade macrophage targeting,” said Krampitz.
Essentially, pancreatic and other tumor types take advantage of this signal to protect tumor cells from elimination by the immune system.
Further pre-clinical studies are needed to establish CD47 as a valid target and to develop further anti-CD47 therapeutic agents for pancreatic and other types of cancers.