By harnessing the very qualities that make sickle cell disease a lethal blood disorder, a research team led by Duke Medicine and Jenomic, a private cancer research company in Carmel, Calif., has developed a way to deploy the misshapen red blood cells to fight cancer tumors.
Reporting in the Jan. 9, 2013, edition of the on-line journal, PLOS ONE, the researchers describe a process of exploiting sickle-shaped red blood cells to selectively target oxygen deprived cancer tumors in mice and block the blood vessels that surround them.
"Sickle cells appear to be a potent way to attack hypoxic (oxygen-starved) solid tumors, which are notable for their resistance to existing cancer chemotherapy agents and radiation," said senior author Mark W. Dewhirst, DVM, PhD, a radiation oncologist and director of Duke's Tumor Microcirculation Laboratory. "This is an exciting finding that suggests a potential new approach to fighting tumors that are currently associated with aggressive disease."
"The very qualities that make sickle cells a danger to people with the inherited genetic disorder can be turned against tumors to fight cancer," said lead author David S. Terman, M.D., head of Molecular Genetics at Jenomic. "Our approach using sickle cells is a novel strategy with broad therapeutic potential that could be directed at breast cancers, prostate cancers, and many other solid tumors that develop resistance to current therapies."
Sickle cells are typically associated with a potentially life-threatening disease in which red blood cells are deformed in the shape of a crescent moon or sickle. Unlike healthy red blood cells that flow smoothly through vessels, the sickle cells get stuck, causing blockages that are painful and damaging to tissue.
A collaborative effort between Duke researchers and scientists from Jenomic began in 2006 to explore whether sickle cells could similarly build clots in the vast networks of blood vessels that feed oxygen-starved, or hypoxic, cancer tumors, which can grow increasingly lethal as their oxygen needs escalate.
In a National Institutes of Health-funded study of mice with breast cancer, the researchers gave the animals an infusion of fluorescently dyed sickle cells and viewed them under special window chambers that provide real-time observation of processes inside the body. Within five minutes, the deformed cells began to adhere to the blood vessels surrounding the hypoxic tumors. Over 30 minutes, the cells had formed clots and began blocking the small blood vessels that fed the tumor.
Dewhirst said the sickle cells stick like Velcro to the hypoxic tumor because it produces an abundance of adhesion molecules as part of its distress from oxygen deprivation. Normal cells don't produce the adhesion molecules, so there's nothing for the sickle cells to snag onto.
"Unlike normal red blood cells, we found that sickle cells show a highly unique natural attraction to oxygen deprived tumors where they stick, cluster and plug tumor blood vessels. Once clustered within the tumor, the sickle cells deposit a toxic iron residue as they die, causing tumor cell death," Terman said.
To boost that caustic effect, the researchers added zinc compounds (zinc protoporphyrin alone or in combination with doxorubicin) to the sickle cells, which caused even greater oxidative stress in the tumor and surrounding blood vessels. This resulted in a dramatic delay in tumor growth, quadrupling the amount of time the tumors were inactive compared to tumors exposed to regular blood cells. Mice showed no acute toxicity to the sickle cell treatment.
"In contrast to drug treatments directed only to the hypoxic tumor cell, our approach uses the inherent qualities of sickle cells to induce injury to the tumor and the vascular micro-environment that feeds the tumor," Terman said.
Dewhirst and Terman said the research team would continue to conduct studies in animals before moving to human trials.
Duke University Medical Center: http://www.dukemednews.org
This press release was posted to serve as a topic for discussion. Please comment below. We try our best to only post press releases that are associated with peer reviewed scientific literature. Critical discussions of the research are appreciated. If you need help finding a link to the original article, please contact us on twitter or via e-mail.
Scientists develop test for three proteins which could give early warning of disease and help doctors distinguish symptoms from chronic pancreatitis
A series of experiments has produced incredible results by giving young blood to old mice. Now the findings are being tested on humans.
A probe inserted into a person's brain can alert intensive-care staff to a critical drop in energy supply, potentially saving the patient's life
Tests that detect changes in genes triggered by drugs could bolster the use of a biological passport – if athletics will spend more on research
The drug derived from the venom of cone snails must be injected into the spinal column to get beyond a patient's blood-brain barrier and bring relief. But scientists think they may have a workaround.
For some unknown reason, the insects that transmit sleeping sickness in sub-Saharan Africa are attracted to the color blue. So scientists think blue flytraps could help wipe out the disease for good.
Pharmacology can get a bad rap in the press. Professors George Davey Smith and David Nutt fight the case for statins and SSRIs.
People who spend time watching fish swim in aquarium tanks could improve their physical and mental wellbeing, a study shows.
The chytrid fungus has wiped out populations of amphibians around the world. A type of the fungus infects only salamanders, and researchers have identified vulnerable areas in North America.
NPR's Melissa Block speaks with the AP's Brazil bureau chief Brad Brooks about the investigation, which found high levels of dangerous viruses in water venues for the 2016 Summer Olympics.