February 23, 2009
Metabolomics Links Compounds to Prostate Cancer
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.
Electron micrograph shows a clump of prostate cancer cells. Image
by Annie Cavanagh. All rights reserved by Wellcome Images.
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.”
