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Duke team finds potential benefit of sickle cells

Cells that cause type of anemia also destroy some hard-to-kill tumors in mice

CorrespondentFebruary 3, 2013 

Mark Dewhirst, a radiation oncologist, director of Duke’s Tumor Microcirculation Laboratory.

Abnormally shaped like crescent moons, sickle cells – deformed red blood cells – cause pain, fatigue and chronic disease. These cells carry less oxygen to the body’s tissues, become stuck in blood vessels, and can break into pieces, interrupting healthy blood flow.

They are responsible for sickle cell anemia, which affects 1 in 12 African Americans, according to the CDC and National Institutes of Health.

But a group of Duke University scientists and the cancer research company Jenomic may have found a beneficial use for these unusual cells.

According to a paper published in January in PLoS One, the team from Duke and Jenomic used sickle cells to kill cancerous tumors in mice.

The study demonstrated that sickle cells could attack “hypoxic” tumors – tumors deprived of oxygen. Such tumors, found in most cancers, can be particularly dangerous.

It is difficult to get chemotherapy drugs to reach them; even those drugs that are able to may not be effective.

“Ironically, hypoxia causes tumors to be more treatment-resistant and aggressive,” said Mark Dewhirst, a radiation oncologist, director of Duke’s Tumor Microcirculation Laboratory and senior author of the paper.

“The tumor cells build up defenses to protect against hypoxia, and the result is worse overall, because such defenses can also protect the tumors from chemotherapy drugs.”

Even radiation therapy, Dewhirst says, may not be successful against hypoxic tumors.

“Radiotherapy causes damage to a cell’s DNA, which can be difficult to fix, if oxygen is present. In the absence of oxygen, the damage is easily fixed. Thus, radiotherapy is less effective on hypoxic cells.”

In their study on mice, the researchers found that sickle cells were attracted to hypoxic tumors, and formed clots in surrounding blood vessels. Eventually, the clotted sickle cells die off; in the process they deposit iron residues that kill the tumors.

“Sickle cells have receptors, which are hidden in normal red blood cells, for molecules produced by hypoxic tumors,” Dewhirst said.

“Also, sickle cells are stiffer than normal red cells, so they are more prone to get hung up.”

Potential uses in humans

If sickle cells are able to kill human tumors, they could eventually be mass-produced and administered to cancer patients.

Additionally, cancer patients would not experience symptoms associated with sickle cell anemia, despite being injected with the cells, Dewhirst said.

“Sickle cell anemia symptoms usually occur after chronic tissue damage over years,” he said. “This would be an acute treatment.”

For now, Dewhirst, along with his team at Duke and in conjunction with Jenomic, plan to conduct further studies on mice.

They hope to eventually move their research into clinical trials. “We are planning to apply for additional grants to pursue other concepts related to this initial series of studies.

“Jenomic wants to commercialize this idea, but there would have to be large-scale production of the cells to do this clinically,” said Dewhirst. “We could not ask sickle cell anemia patients to donate blood for this purpose – it would be unethical.”

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