Mast Cells and Cancer Cells Share Common Pumping Mechanism

Researchers have identified a mechanism that explains how the lipid messenger sphigosine-1-phosphate (S1P) is released from mast cells.

Mast cells are specialized cells that react to allergy-causing agents by releasing substances that trigger the body's allergic response. S1P, which has a regulatory effect on cell survival and motility, angiogenesis, and inflammatory responses, is one of major interest.

Investigators at Virginia Commonwealth University (Richmond, USA) found that S1P was exported from mast cells independently of their degranulation and demonstrated that ATP-binding cassette (ABC) transporters mediated this release. ABC transporters are known to play a crucial role in the development of multi-drug resistance (MDR). In MDR, patients who are on medication eventually develop resistance to not only the drug they are taking, but to several different types of drugs. This is caused by several factors, one of which is increased excretion of the drug from the cell by ABC transporters. One of the findings in the current study, which was published in the October 18, 2006, online edition of the Proceedings of the [U.S.] National Academy of Sciences, showed that the same drugs that prevented cancer cells from pumping out chemotherapeutic drugs blocked export of S1P.

Senior author Dr. Sarah Spiegel, professor of biochemistry at Virginia Commonwealth University, said, "Our study shows that mast cells can use a special kind of transporter that has long been known to be used by cancer cells to push anti-cancer drugs out and help them survive the treatment. Our study is the first to establish a mechanism by which S1P can be exported out of mast cells and perhaps by cancer cells as well.”



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