February 23, 2009

Metabolomics Links Compounds to Prostate Cancer

Several lumpy round cells ctron micrograph shows a clump of prostate cancer cells. Image by Annie Cavanagh.Wellcome Images.

A new study has uncovered a molecule associated with the transformation of benign prostate tissue into metastatic prostate cancer. The discovery identifies a potentially useful indicator for the disease and suggests new targets for prostate cancer treatments.

Scientists have extensively studied the genes and proteins involved in the development and progression of human tumors. The relatively new field of metabolomics takes a different approach, focusing on the products of chemical reactions throughout the body, called metabolites. Metabolomics captures snapshots of the body’s physiological state at given points in time, giving researchers insights into the chemical pathways involved in disease.

A team led by researchers at the Michigan Center for Translational Pathology in Ann Arbor set out to use metabolomics to characterize the progression of benign prostate tissue to prostate cancer. Using a technique called mass spectrometry, which sorts chemical compounds by their molecular weights, the researchers profiled more than 1,126 metabolites from 262 clinical samples related to prostate cancer (42 were tissue samples, 110 urine samples and 110 samples of blood plasma). Their work was supported in part by NIH’s National Cancer Institute (NCI).

The researchers reported in the February 12, 2009, issue of Nature that the metabolomic profiles enabled them to distinguish between benign prostate tissue, clinically localized prostate cancer and metastatic prostate cancer. They identified 60 metabolites in prostate tumors that weren’t present in benign prostate tissue. The levels of 6 of these metabolites increased with the progression from benign prostate tissue to localized cancer and metastatic disease.

One of these metabolites, called sarcosine, was greatly elevated during the progression to metastasis. When the researchers tested urine samples, they found that sarcosine could be detected in the urine of men with prostate cancer, making it a potentially useful marker for cancer progression.

To further explore sarcosine’s role, the researchers turned to laboratory-grown cells. As expected, sarcosine levels were higher in invasive prostate cancer cells than in benign prostate cells. When the researchers added sarcosine to benign prostate cells, they found that it caused the cells to become invasive. By manipulating the levels of enzymes that regulate sarcosine metabolism, the scientists were able to control the invasiveness of benign and malignant prostate cells.

“Components of the sarcosine pathway could serve as novel avenues for therapeutic intervention,” said lead scientist Dr. Arul M. Chinnaiyan. “Our next step will be to confirm these findings in a greater number of specimens and to have our results validated by other laboratories.”

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