Metabolomics against cancer
Alexey Levin, Voice of America
Prostate cancer is a very insidious disease. In principle, its diagnosis does not pose any particular problems. The doctor may suspect the occurrence of a tumor based on measuring the concentration of one of the plasma proteins, prostate-specific antigen. The production of this enzyme, which is secreted by prostate epithelial cells, increases with the increase in the size of the gland. Such an increase may be quite benign, but it can also be explained by the appearance of a cancerous tumor. After receiving an alarm signal from the laboratory, the doctor can probe the prostate through the rectum, look at it through a fiber-optic probe that is inserted into the bladder, or send the patient for an ultrasound examination. These methods together make it possible to reliably detect prostate tissue seals, which may turn out to be cancerous foci.
However, the very identification of such seals is still half the battle. The fact is that prostate tumors can develop very slowly, do not give any symptoms and do not actually require medical intervention – especially in old age. However, some tumors, including asymptomatic ones, quickly give birth to metastases in the kidneys and bones, which greatly complicate treatment and often lead to death. To determine the aggressiveness of the tumor, it is necessary to take tissue samples from several areas of the gland and send them for histological analysis. Only in this way can a doctor make a final diagnosis of the disease.
Prostate biopsy is a reliable technique, but by no means cheap. In addition, it is clearly not suitable for the initial mass examination of men for prostate cancer. It would be much better to detect aggressive prostate cancer based on biochemical blood or urine tests. Unfortunately, this blue dream of urologists is still far from being realized. However, in recent years, the results of several studies have been published, which allow us to hope that this problem is completely solvable.
A report on another such work appeared in the journal Nature on February 12. It was performed by the staff of the University of Michigan in Ann Arbor, which has now become one of the leading American centers for the search for new methods of oncological diagnosis. The study was conducted under the supervision of Professor of Pathology and Urology Arul Chinnaiyan, who also heads the University Center for Oncological Bioinformatics.
The Michigan scientists worked as part of a new research strategy called metabolomics. This term is not yet as well known as genomics, the study of genes, or proteomics, the study of intracellular proteins. It sounds rather strange, but only because of the novelty. Since school days we know (or at least we should know) what is metabolism. In a broad sense, it is just a metabolism, in a more special sense, it is the totality of all biochemical reactions occurring in living cells. The intermediates that are formed during such reactions are called metabolites. Metabolomics is engaged in their research.
Professor Chinnayan and his colleagues have set themselves a very bold task. They decided to identify, if possible, all the metabolites that arise during the work of the prostate gland, and then select those that could be convincingly associated with its malignant tumors. As a starting material, they used both sections of prostate tissue and urine and blood samples taken from patients with diagnosed prostate cancer. Using the latest gas and liquid chromatographs and mass spectrometers, the experimenters isolated 1126 different metabolites from these samples.
Over 90% of these substances were produced during the vital activity of normal cells, but 87 metabolites originated in tumor tissues. However, most often they were present in such quantities that they were not allowed to be used as cancer markers. However, after careful sifting, the scientists selected six metabolites that were quite suitable for this. There were noticeably more of them in the cells of localized tumors than in the cells of healthy tissues, and even more in the cells of metastases.
Scientists were particularly interested in one of these substances – sarcosine, aka N-methylglycine. This is a fairly simple compound, its molecule consists of only three carbon atoms, one nitrogen atom, two oxygen atoms and seven hydrogen atoms. In normal cells, it was practically absent, however, it was contained in 42% of cells of localized tumor foci and in 79% of cells of metastases. Laboratory experiments have shown that this substance promotes the transformation of normal prostate cells into metastatic cancer cells. The researchers also suspect that sarcosine increases cell mobility and thus again contributes to the appearance of secondary tumors. Therefore, they consider it their main candidate for use as a label for aggressive prostate cancer. Michigan scientists expect to develop a simple urine test that will allow inexpensive and reliable measurement of sarcosine levels.
However, it is not necessary to talk about the imminent clinical application of this technique yet. To make sure of the diagnostic effectiveness of the sarcosine test, it will take a long time to study the metabolism of prostate cancer patients, and not dozens of people who were followed by researchers from Michigan, but hundreds and thousands. It is quite possible that along the way it will be possible to identify other markers of aggressive cancer that will have all the advantages over sarkosin. So metabolomics has yet to show what it is capable of.
Portal "Eternal youth" www.vechnayamolodost.ru13.02.2009