Stem cells are the cause of ovarian cancer
Cancer inside stem cells
Scientists from MIPT have solved the mechanism of ovarian cancer:
it originates in the stem cells of the epitheliumAlexandra Borisova, "Newspaper.
So far, this result has been obtained in mouse models, but scientists hope to find a similar mechanism in humans and use it for treatment. About the work "Newspaper.Ru" was told by one of its authors, megagrant laureate Grigory Enikolopov.
Ovarian cancer is the fifth most common cause of cancer death in women, the leading cause of death from gynecological malignant tumors and the second most common tumor diagnosis in gynecology. In Russia, the incidence of ovarian cancer is approximately 77 cases per 100 thousand population. However, the pathogenesis of this disease and the mechanism of its development are still poorly studied. Previously, scientists managed to find out that cancers of the epithelium – the layer of cells lining the surface and internal organs of the body – occur either at the border of two types of cells, or in stem cells of epithelial tissue. A Russian-American team of scientists has discovered dangerous stem cells in the ovarian epithelium.
About this work "Newspaper.Ru" was told by one of her co-authors, a Russian-American neuroscientist, professor of the famous Cold Spring Harbor laboratory, Grigory Enikolopov, who created a laboratory at the Moscow Institute of Physics and Technology (MIPT) with the funds of a megagrant.
– What is the essence of your work?
– The main result of the study published in the journal Nature (Ovarian surface epithelium at the junction area contains a cancer-prone stem cell niche) is the discovery of a new very small population of stem cells in the ovaries. These are so-called tissue-specific stem cells that exist in various tissues. Unlike embryonic stem cells, from which all the cells of the body then emerge, such cells are more specialized and in a normal situation generate only a few specialized types of cells to maintain the corresponding tissue or organ. Firstly, it turned out that these cells heal damage to the ovary after each release of the egg: the egg is a very large formation, and there is almost a small tissue rupture, which then needs to be healed.
Secondly, it turned out that these cells are particularly susceptible to malignant transformation and generate tumors, which, when transplanted, generate new tumors (we work with model organisms - mice). Scientists have long suspected that somewhere in this area there may be cells from which an ovarian tumor grows, and we have now managed to identify these cells.
– What was done specifically by Russian scientists at MIPT? What methods were used in this case?
– The work was carried out by the group of the leader of this project, Alexander Nikitin from Cornell University, together with our group at MIPT. For the project, we used very sophisticated genetic schemes of animal crosses and methods of visualization of stem cells and their offspring. Such models and methods are at the center of our group's work at MIPT and the Kurchatov Institute. They require sophisticated microscopic equipment, possession of the latest genetic and cytological methods for obtaining new animal lines.
– What is the practical application of the results obtained by you and your colleagues?
– Our work was carried out on the classical model of human diseases – mice. But, of course, we hope that the knowledge gained from this model will also be important for the treatment of cancer in humans. Firstly, having found the main characteristics (markers) of this very small group of cells, we hope to use the same markers to find the corresponding cell population in human tissues. Secondly, knowing what to monitor, we will be able to understand whether such cells, after some changes, are the source of ovarian cancers in humans. Thirdly, we will be able to use these cells for screening drugs that could prevent their uncontrolled reproduction or prevent malignant transformation. Finally, similar cell types in other tissues may be the source of other types of tumors, such as cervical cancer or esophageal cancer, for which suspicions are accumulating that a similar very small and unusual population of stem cells may serve as a source of malignant tumors.
– Please tell us more about the international team of scientists who worked on the article.
– We have been cooperating with Alexander Nikitin from Cornell University for several years. Alexander is the leader of this project and the main author of the article. He is a completely unique specialist in cancer cell transformation, who has done a lot in this field and has recently taken up stem cells. We are involved in various projects together and I am sure we will continue this cooperation. It is important to understand the laws by which these and other types of stem cells "decide" whether to remain dormant, whether to start dividing, whether to migrate to some other part of the tissue, whether to turn into other types of cells, and so on. And the most important thing is to understand why exactly these cells turn into cancerous cells so easily and whether this knowledge can be used to prevent malignant growth or develop drugs.
– What role did megagrant play in this work?
– Megagrant allows you to develop new areas that require the latest and very expensive equipment, perform complex and expensive genetic research, create new models for studying stem cells and train employees. The main task is to create an actively working group that would be able to set and solve problems of the most complex order, would be ready to commercialize its ideas and, most importantly, would help other stem cell groups in the country.
– What are your general impressions about the megagrant program?
– Impressions are ambiguous. On the one hand, there is a huge trust in transferring such large sums to the practically scientific discretion of a leading scientist, and on the other hand, there are completely suffocating rules for spending them and a short–sighted strategy. At the same time, the administrators I have to deal with, both at MIPT, at the Kurchatov Center, and at the ministry, are absolutely wonderful and try to help our group in everything. But laws and regulations practically do not allow rational use of the funds that we have.
Examples are in everything: it will take from three months to six months to buy a reagent that is needed for work immediately (I will need a maximum of two days in my American laboratory); nothing can be bought directly and it is necessary to act through intermediary firms that slow down purchases and inflate prices; it is impossible to order service–type work abroad (namely, for such work, accelerating research and reducing the cost of their implementation, I spend most of the funds in the American laboratory); all financial activities must be completed in a few months – between the belated arrival of money and the need to write an annual report; finally, the reports themselves are hundreds of pages of text, whose writing completely stops the work of several people (for such an annual report to the National Institutes of Health, I am writing three (!) pages of text).
To put it even more simply, we are buying appliances that will remain, and creating infrastructure that will also remain; but our efficiency could be much greater.
– Are you experiencing problems with the extension of funding?
– Extension of grants is a separate conversation. The group is only "warming up", in biology it takes more than one year to create an actively working and self–sustaining group. To end funding in two years and transfer the group to foot food is an extreme waste, the purchased devices will be idle, the planned experiments will slow down sharply, and talented employees will not be able to realize their potential. And, mind you, we are talking about the best university and the leading scientific center of the country, about the strongest employees and students recruited into the group, and about the situation of exceptional support and goodwill from the administration. By and large, the megagrant program would have to play the role of a sensor with which you can find ways to clear blockages and ossified rules, and then a battering ram with which to eliminate these blockages; in my opinion, this huge potential is realized only by a small fraction. The hope is that now funding for science is increasing, and several different funding formats for the strongest groups are emerging in the country, and that this critical mass of scientists will be able to create a rational model for organizing and supporting science.
Portal "Eternal youth" http://vechnayamolodost.ru07.03.2013