Breast cancer: we know how to stop metastases
Scientists have found the "culprit" of the formation of metastases
Natalia Bykova, STRF.ru
A scientific group from the University of California San Diego Medical School has experimentally shown for the first time that immune system cells contribute to the growth of breast cancer metastases. Experts have proposed a way to slow down this process. Tests have so far been carried out on mice, but scientists hope that this discovery will help create a drug that is effective in the late stages of breast tumor development in humans. An article on the results of the study was published in the journal Nature (Wei Tan et al., Tumour-infiltrating regulatory T cells stimulate mammary cancer metastasis through RANKL–RANK signaling).
The Laboratory of Gene Regulation and Intracellular Signal Transmission (Laboratory of Gene Regulation and Signal Transduction) from the Medical School of the University of California San Diego has been engaged in research in the field of oncological diseases for more than 25 years. Her fame in scientific circles was provided by works showing the role of the immune system in the development of cancer. As a result of these studies, a number of potential drugs have been found that can be used for the prevention and treatment of cancer, as well as autoimmune diseases. Independent scientific studies have already confirmed that the immune system can participate in the process of tumor formation, as well as contribute to their growth and the acquisition of malignancy. However, it was still unclear whether the cells of the immune system can provoke the formation and growth of metastases, which pose a much greater threat than the tumor itself, because more than 90 percent of cancer patients die from metastasis, and not from the growth of the primary tumor. The answer to the question of the relationship between the cells of the body's immune system and the formation of secondary foci of cancer was precisely what scientists from San Diego tried to find in their study. The subject of their study was the late stages of breast tumor development. The relevance of this study lies in the fact that breast cancer ranks second after lung cancer in the statistics of mortality from malignant neoplasms.
About 1 million women get breast cancer every year in the world. This is the most common type of malignant neoplasm among all types of cancer in women. According to Rosstat, in Russia in 2008, this type of tumor was first detected in 52,500 women. Over a 10-year period, the number of cases of breast cancer in the Russian Federation has increased by almost 15 thousand. The highest incidence rates were noted in large cities such as Moscow, St. Petersburg, Khabarovsk, Rostov, Kaliningrad, Ryazan
One of the co-authors of this work, our compatriot, a graduate of Lomonosov Moscow State University, a former researcher at the V. A. Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences Sergey Grivennikov, said STRF.ru how the research was conducted:
"We transplanted breast tumor cells to laboratory mice. In some experimental animals, the IKK-alpha protein molecule (Inhibitor of nuclear factor kappa-B kinase subunit alpha) was “turned off” in cancer cells. This protein is part of a complex protein complex that performs an important function of controlling the work of other proteins, and as a result regulates the most important cellular processes, such as the immune response, cell division and their death.
Comparisons with the control group of animals showed that metastases in the lungs develop quite quickly in ordinary mice, and in their counterparts with IKK-alpha molecules “turned off”, the process of formation and growth of metastases significantly slowed down. Based on previous studies, we knew that in order to perform its functions, IKK-alpha must first be put into an active working state by various signals coming from neighboring cells. We conducted a detailed search for specific molecules that activate IKK-alpha in our model, and as a result we found the RANKL molecule.
RANKL is a well–studied protein. The greatest amount of it is noted in the bone tissue. Under normal conditions, throughout our lives, this protein participates in the regulation of metabolism in bone tissue and promotes proper bone growth, ensuring balance – so that bones are strong, but not brittle. In addition, it is able to stimulate the growth of breast cells during lactation. This molecule also plays a key role in the development of diseases such as osteoporosis and arthritis, when the formation of the RANKL protein in the body gets out of control. There is already a drug – monoclonal antibodies that can resist this undesirable effect of RANKL, that is, to suppress the development of osteoporosis in women after 50 years and bone metastases in patients with prostate cancer. RANKL, apparently, also has an important ability to change the behavior of cancer cells, making them more mobile and forcing them to migrate and form new foci of the disease, as well as increases the resistance of cancer cells and enhances the process of their division and secondary tumor growth
The discovery turned out to be that we were able to determine which cells produce RANKL – these are the immune cells of the body – the so-called T-regulatory lymphocytes, which, with the normal functioning of the body, are designed to protect us from the development of autoimmune diseases, such as multiple sclerosis, Crohn's disease and others. In our experiment with breast cancer, these T lymphocytes played a bad role - they produced a RANKL molecule that bound to its RANK receptor on the surface of cancer cells and made them more capable of metastasis. In this work, we inhibited (suppressed) the synthesis of RANKL and its RANK receptor and found out that breast tumor metastases to the lungs are also inhibited," Sergey explained. – While specific inhibitors of the function of IKK-alpha that can be used to treat people have not yet been developed, we can control the process of inactivation (“shutdown”) of IKK-alpha in cancer cells by using an already created drug used to suppress the work of the RANKL protein in diseases of bone tissue, but not previously used for the treatment of breast cancer. The following question remains unclear: what causes our T-regulatory lymphocytes to behave in this way, and the answer most likely lies in the ability of cancer cells to produce special protein factors that cause T-lymphocytes in the tumor to produce RANKL."
Thus, scientists have shown for the first time that the immune system can activate the process of metastasis of breast cancer, and have found how to suppress and slow down this process. Whether open patterns will work in clinical trials remains to be seen in the course of new research. The authors are inclined to believe that experiments with the participation of volunteers will also give positive results. If their assumptions are confirmed, pharmacological firms will work on creating a drug for the prevention and treatment of breast tumor metastases.
Portal "Eternal youth" http://vechnayamolodost.ru12.05.2011