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Breaking the mucus barrier unveils cancer cell secrets

17.03.2011
Measuring the mechanical strength of cancer cell mucus layers provides clues about better ways to treat cancer, and also suggests why some cancer cells are more resistant to drugs than others, according to Kai-tak Wan, associate professor of engineering at Northeastern University, Boston, Mass.

According to Wan, healthy tissues naturally secrete mucus to protect against infection. Cancer cells, however, produce far more mucus than healthy cells.

Mucus consists of protein "stalks" attached to sugar sidechains, or "branches." This tangled brush forms a physical barrier. When over-expressed, it can prevent drugs from reaching the cancer cells beneath. Over-expressed mucus also makes it easier for cancer cells to break away from surrounding cells and move through the body, or metastasize.

Wan's research partner, Robert B. Campbell, an associate professor of pharmaceutical sciences at Massachusetts College of Pharmacy and Health Sciences, Worcester, Mass., is investigating the use of chemical agents that limit the formation of this tangled mucus barrier so medicines can get through.

To determine how well those agents work, Wan used the nanoscale tip of an atomic force microscope to push against the mucus barrier. The less resistance it encountered, the less tangled the barrier.

Wan found that suppressing the formation of mucus sidechains significantly reduced the energy needed to pierce the mucus barrier in lung, breast, colorectal, pancreatic, and wild type (natural) ovarian cancer cells.

Yet the treatment registered barely any change in multi-drug resistant ovarian cancer cells. No one understands how those cells resist drugs that ordinarily kill wild type ovarian cancer.

Wan's research points to an important difference. The mucus layer formed by the two types of cells reacts differently to the same chemical treatment.

"How this phenomenon is related to biochemistry is unknown at this stage, but it tells us what we should be looking at in future research," Wan said about his and Campbell's conclusions.

The article, "Glycoprotein mucin molecular brush on cancer cell surface acting as mechanical barrier against drug delivery" by Xin Wang, Aalok A. Shah, Robert B. Campbell, and Kai-tak Wan appears in the journal Applied Physics Letters. See: http://link.aip.org/link/applab/v97/i26/p263703/s1

Journalists may request a free PDF of this article by contacting cblue@aip.org

ABOUT APPLIED PHYSICS LETTERS

Applied Physics Letters, published by the American Institute of Physics, features concise, up-to-date reports on significant new findings in applied physics. Emphasizing rapid dissemination of key data and new physical insights, Applied Physics Letters offers prompt publication of new experimental and theoretical papers bearing on applications of physics phenomena to all branches of science, engineering, and modern technology. Content is published online daily, collected into weekly online and printed issues (52 issues per year). See: http://apl.aip.org/

ABOUT AIP

The American Institute of Physics is a federation of 10 physical science societies representing more than 135,000 scientists, engineers, and educators and is one of the world's largest publishers of scientific information in the physical sciences. Offering partnership solutions for scientific societies and for similar organizations in science and engineering, AIP is a leader in the field of electronic publishing of scholarly journals. AIP publishes 12 journals (some of which are the most highly cited in their respective fields), two magazines, including its flagship publication Physics Today; and the AIP Conference Proceedings series. Its online publishing platform Scitation hosts nearly two million articles from more than 185 scholarly journals and other publications of 28 learned society publishers.

Charles E. Blue | EurekAlert!
Further information:
http://www.aip.org

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