In many types of cancer cells from the primary tumor can intravasate into the bloodstream as circulating tumor cells or CTCs. These CTCs can then interact with the receptor-bearing endothelial cell wall. The process is similar to leukocyte extravasation – the flow of blood or lymph-fluid into surrounding tissue during inflammation.
Now for the first time biomedical engineers at Cornell University inIthaca in New York, NY have discovered a new way to destroy these metastasizing cancer cells traveling through the bloodstream by hitching cancer-killing proteins along for a ride on life-saving white blood cells. [1][2]
Metastases involved in majority of cancers deaths
“These circulating cancer cells are doomed,” said Michael King,Ph.D, professor of biomedical engineering Cornell and the study’s senior author. “About 90% 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.”
? 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…
Problematic approach
“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 cancers problematic,” King noted.
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 with the E-selectin protein was able to stick to leukocytes ? white blood cells ? abundant in the bloodstream. When a cancer cell comes into contact with TRAIL, which is nearly unavoidable in the frenzied flow of blood, the cancer cell essentially kills itself.
Unexpected and surprising
“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,” Kind said.
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% 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 that mimicked human-body conditions, however, the success rate in killing the cancer cells jumped to nearly 100%.
For more information
[1] Mitchell MJ, Wayne E, Rana K, Schaffer CB, King MR. TRAIL-Coated Leukocytes that Kill Cancer Cells in the Circulation. Proc Natl Acad Sci U S A. 2014, January. [Article]
[2] Rana K, Liesveld JL, King MR. Delivery of apoptotic signal to rolling cancer cells: a novel biomimetic technique using immobilized TRAIL and E-selectin.Biotechnol Bioeng. 2009 Apr 15;102(6):1692-702. doi: 10.1002/bit.22204.[Article][PubMed]
Graphic 1:The?Unnatural?Killer?Cells?concept:?nanoscale?liposomes?with?TRAIL?protein?(in?green)?attach?to?the?surface?of?white?blood?cells,?and?are?available?in?the?blood?flow?to?bump?into?cancer?cells?and?program?them?to?die. Photo: Michael King,Ph.D, professor of biomedical engineering Cornell.
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