Nanomedicine  

Researchers have isolated a protein that causes metastasized tumors to implode at contact. Because the majority of death caused by cancer are the result of metastasized tumors, this development could go a long way in treating cancer.

By attaching a cancer-killer protein to white blood cells, Cornell University biomedical engineers have demonstrated the annihilation of metastasizing cancer cells traveling throughout the bloodstream.

The study, “TRAIL-Coated Leukocytes that Kill Cancer Cells in the Circulation,” was published online in the journal Proceedings of the National Academy of Sciences.

“These circulating cancer cells are doomed,” said Michael King, Cornell professor of biomedical engineering and the study’s senior author. “About 90 percent of cancer deaths are related to metastases, but now we’ve found a way to dispatch an army of killer white blood cells that cause apoptosis – the cancer cell’s own death – obliterating them from the bloodstream. When surrounded by these guys, it becomes nearly impossible for the cancer cell to escape.”

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Metastasis is the spread of a cancer cells to other parts of the body. Surgery and radiation are effective at treating primary tumors, but difficulty in detecting metastatic cancer cells has made treatment of the spreading cancer problematic, say the scientists.

King and his colleagues injected human blood samples, and later mice, with two proteins: E-selectin (an adhesive) and TRAIL (Tumor Necrosis Factor Related Apoptosis-Inducing Ligand). The TRAIL protein joined together with the E-selectin protein stick to leukocytes – white blood cells – ubiquitous in the bloodstream. When a cancer cell comes into contact with TRAIL, which becomes unavoidable in the chaotic blood flow, the cancer cell essentially kills itself.

“The mechanism is surprising and unexpected in that this repurposing of white blood cells in flowing blood is more effective than directly targeting the cancer cells with liposomes or soluble protein,” say the authors.

In the laboratory, King and his colleagues tested this concept’s efficacy. When treating cancer cells with the proteins in saline, they found a 60 percent success rate in killing the cancer cells. In normal laboratory conditions, the saline lacks white blood cells to serve as a carrier for the adhesive and killer proteins. Once the proteins were added to flowing blood, which models forces, mixing and other human-body conditions, however, the success rate in killing the cancer cells jumped to nearly 100 percent.

As this research is newly announced, King says animal trials will continue and he hopes that the research will proceed to human clinical trials sometime in the future.



SOURCE  Cornell University

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 Cancer Research  

A new study by a team of researchers from the University of Notre Dame provides an important new insight into how cancer cells are able to avoid the cell death process. The findings may suggest a chemotherapeutic approach to prevent the spread of cancers.

Anew study by a team of researchers from the University of Notre Dame provides an important new insight into how cancer cells are able to avoid the cell death process. The findings may reveal a novel chemotherapeutic approach to prevent the spread of cancers.

The paper appears in the current issue of the journal Cancer Research, which is the most frequently cited cancer journal in the world.

Metastasis, the spread of cancer from one organ to other parts of the body, relies on cancer cells’ ability to evade a cell death process called anoikis, according to Zachary T. Schafer, Coleman Assistant Professor of Cancer Biology at Notre Dame.

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Metastasizing cancer cells are able to block anoikis, which normally results from detachment from the extracellular matrix. However, Schafer notes that the molecular mechanisms that cancer cells detached from the extracellular matrix use to survive have not been well understood.

“This paper reveals that cancer cells that are detached from their normal environment, as they would be during metastasis, rely on the activity of antioxidant enzymes to facilitate their survival,” Schafer said. “This class of enzymes is critical for neutralizing oxidative stress and function much like the antioxidant compounds that are present in a variety of healthy foods.”

The paper describes a prominent role for antioxidant enzymes in facilitating the survival of breast cancer cells after detachment from the extracellular matrix. Conversely, the researchers report, silencing antioxidant enzyme expression reduced tumor formation.

“The results in this paper suggest that targeting antioxidant enzymes with novel therapeutics may selectively kill off metastasizing cancer cells,” Schafer said.



SOURCE  University of Notre Dame

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