February 22, 2008

Aliquots — Research highlights from VUMC laboratories

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Forecasting tumor spread

A deadly trait of cancer cells is their ability to invade neighboring tissues and move — metastasize — to new sites in the body. To develop models that can predict how and when a tumor will spread, investigators require laboratory tools to measure how cancer cells move along various patterns of proteins.

John Wikswo, Ph.D., and colleagues have developed a new way of depositing protein for studies of cell movement. The method, featured on the cover of the February issue of Lab on a Chip, uses computer-driven microfluidic devices that can be readily altered to produce varying protein profiles.

The new process will enable real-time live cell imaging studies of normal and cancer cell movement, generating crucial data for the development of mathematical models of cancer invasion. Such models might in the future be used to “forecast” a tumor's progression and help physicians decide what course of treatment to pursue.

— Leigh MacMillan

Drug response: an individual thing

The blood pressure-lowering drug clonidine works better for white than for black Americans. Genetic variations in clonidine's target, the alpha-2 receptor, or its signaling mechanisms might contribute to these ethnic differences. But clonidine also activates other receptors, which could affect responses to it.

C. Michael Stein, M.D., and colleagues explored ethnic differences and the contribution of genetic variations to responses to dexmedetomidine (dex), a more highly selective alpha-2 receptor drug. The investigators measured blood pressure, heart rate, and blood catecholamine levels following dex infusions in 73 healthy subjects. They report in the February issue of Hypertension that there were marked interindividual differences in the responses to dex, but that there were no differences between the groups of black and white subjects. They further found that neither of two genetic variants they examined affected responses to dex, suggesting that other genetic and/or non-genetic factors affect how individuals respond to alpha-2 receptor drugs.

— Leigh MacMillan

Fertile ground for some tumors

Tumors and their host environments are often likened to “seed” and “soil”: tumors require a hospitable environment to grow and spread through the body. Mary Zutter, M.D., and colleagues are examining how one type of “soil,” a component expressed by blood vessels called alpha2-beta1 integrin, influences tumor growth and angiogenesis in mice.

They found that, compared to normal mice, mice lacking this integrin have increased angiogenesis and tumor growth when injected with melanoma cells, but not when injected with lung cancer cells. This differential response, they show, is due in part to increased secretion of a growth factor by the melanoma tumors but by not lung tumors.

The results, reported in the February issue of Blood, show that tumor angiogenesis depends on specific interactions between the tumor cell and the integrin “repertoire” of the host microenvironment. The authors suggest that these integrin-deficient mice are an example of genetic alteration of the “soil” determining response to the “seed.”

— Melissa Marino

Mouthwash test for cancer risk

Aside from advancing age or a history of tobacco use, there are currently few predictors of an individual's risk for developing head and neck cancers. Since cancer is caused by mutations in DNA, Robbert Slebos, Ph.D., and colleagues investigated the general mutational load in an easily accessible clinical sample — cells obtained by mouth rinse.

They found that mutations in a “microsatellite” marker in DNA increased with age, but smoking had no influence. Also, individuals who had head and neck cancer that was cured by surgery showed higher mutation frequencies than controls.

The results confirm earlier studies showing that microsatellite mutations increase with age, and provide evidence that these mutations may be increased in cancer patients.

The study, appearing in the February issue of the British Journal of Cancer, suggests that assays measuring microsatellite mutations may be become useful tools to estimate cancer risk in the future.

— Melissa Marino

We welcome suggestions for research to highlight in Aliquots. The items should be primary research articles (no reviews, editorials or commentaries) published within the last two months in a peer-reviewed journal. Please send the article citation (PDF if available) and any other feedback about the column to: aliquots@vanderbilt.edu.

Past Aliquots

June 22, 2012
June 8, 2012
May 11, 2012
April 27, 2012
April 13, 2012
March 30, 2012
March 16, 2012