The study, conducted in mice and published
"Our research translates mechanistic insights about heparin into a potential new therapy for neuroblastoma, and possibly other cancers," said senior author
Neuroblastoma is a cancer that arises in nerve tissue, and is typically seen in infants and children. While neuroblastoma is rare overall - 700 new cases in
Despite numerous treatment options for neuroblastoma, survival rates in children with advanced cancer are less than 40 percent due to disease recurrence and the persistence of residual cancerous cells after chemotherapy. However, one difference between neuroblastoma and other solid tumors is the function of the stroma, or connective tissue around the tumor.
"Most of the time we think of stroma in solid tumors as a bad thing that helps cancers become more invasive. In neuroblastoma, it's the opposite: having a lot of connective tissue around the tumor does something favorable for patients," Blobe said.
Studying the stroma's biology, the researchers determined that the connective tissue produces and releases receptors involved in nervous system signaling called heparan sulfate proteoglycans. The heparan sulfate proteoglycans had a differentiating effect on the cancer cells, making immature cancer cells act more like mature neurons and keeping them from proliferating.
Heparan sulfate proteoglycans are structurally similar to the anticoagulant heparin, which led the researchers to hypothesize that heparin might recreate the function naturally occurring in the stroma. They administered heparin to human neuroblastoma cells in laboratory cultures as well as to mice with neuroblastoma, and found that it could differentiate cancer cells and cause tumors to regress in mice. However, the heparin caused severe bleeding, rendering it an unusable treatment.
"That's what caused the 'eureka' moment. Heparin was effective, but caused serious bleeding," said
The researchers studied the structure of heparin, and determined that although certain properties were necessary for anticoagulation, only some were important for the signaling that promoted differentiation. Using this finding, they identified a derivative of heparin that would still allow for differentiation but not cause anticoagulation.
When tested in lab cultures, the heparin derivative suppressed neuroblastoma growth. In mice, it slowed the cancer's progression, shrunk the tumors and extended the animals' lives.
"The study illustrates the benefit of listening to the cancer and its biology," Knelson said. "We started out with an investigation of tumor stroma and its mechanism, and designed a potential therapy using this new understanding."
The team is now working to move the research into clinical trials in humans to determine whether the heparin derivative offers the same benefit in humans as it did in mice.
"We want to repurpose a drug that's already out there for the benefit of patients," Blobe said. "What's exciting about that is there are other tumors in which differentiation is useful, so there's the potential to apply these insights to other cancers."
Keywords for this news article include: Cancer, Oncology, Hematology, Pediatrics, Neuroblastoma, Heparin Therapy,
Our reports deliver fact-based news of research and discoveries from around the world. Copyright 2014, NewsRx LLC
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