iPSCs and cancer cells are similar at the molecular level
Significant similarity of induced pluripotent stem cells and cancer cells has been established
LifeSciencesToday based on materials from the University of California – Davis:
UC Davis researchers find multiple similarities between cancer cells and induced pluripotent stem cellsScientists at the University of California at Davis have found new evidence that the type of stem cells currently being considered as a promising treatment for various diseases is very similar to the type of cells that give rise to cancer.
The findings suggest that although these cells – known as induced pluripotent stem cells (iPSCs) – are quite promising for the treatment of a wide range of diseases and injuries, scientists and doctors should be very cautious about any use of them as a clinical method, as iPSCs can lead to the development of cancer.
An article about the study (Induced pluripotency and oncogenic transformation are related processes) is published in the journal Stem Cells and Development.
"This is the first study that describes specific molecular pathways common to iPSCs and cancer cells when they are directly compared," says study leader Paul Knöpfler, PhD, associate professor of cell biology and human anatomy. "This means that much more research needs to be done before iPSCs can be used clinically. Nevertheless, our work expands the existing knowledge base, which will not only help make stem cell treatment safer, but also gives us a new understanding of the process that causes cancer and more effective ways to combat this disease."
In 2007, cell biologists learned how to "force" specialized, differentiated cells (for example, skin cells or muscles of an adult) to transform into induced pluripotent stem cells. Like embryonic stem cells, iPSCs are a type of stem cells that can become cells of any tissue. This "pluripotency" means that iPSCs can be used to treat various human diseases by applying a fundamentally new method of therapy known as regenerative medicine.
For scientists and doctors, iPSCs are of particular interest, since obtaining them avoids the ethical disputes that are constantly being conducted around embryonic stem cells. In addition, induced pluripotent stem cells can be obtained from the patient's own skin, which eliminates the possibility of an immunological conflict that occurs when cells are transplanted from a donor to a recipient. Unlike therapy based on embryonic stem cells, iPSCs eliminate the need to prescribe immunosuppressive drugs to patients that suppress their immune system.
Earlier studies have shown that both embryonic stem cells and iPSCs pose certain health risks. An increasing body of evidence suggests that pluripotency may be associated with the rapid cell growth characteristic of cancer. Scientists are well aware that both induced pluripotent and embryonic stem cells are capable of giving rise to teratomas – an unusual type of benign tumors consisting of many different types of cells. The study by Dr. Knepfler and his colleagues shows for the first time a significant similarity of iPSCs, as well as embryonic stem cells, with malignant cells.
The researchers compared induced pluripotent stem cells with a form of malignant cells known as oncogenic foci (oncogenic foci, OF), which are also obtained in laboratories. These types of cells are used by oncologists to create models of malignant tumors, in particular, sarcomas. Scientists compared transcriptomes of these different cells, consisting of RNA molecules, or "transcripts". Unlike DNA analysis, which reflects the entire genetic code of a cell regardless of the activity of its genes, transcriptomes reflect only those genes that are actively expressed at a given time, and therefore give an idea of the actual cellular activity.
Based on the analysis of transcriptomes, the researchers found that induced pluripotent stem cells and malignant sarcoma cells are similar in many respects. When comparing the transcriptomes of iPSCs and oncogenic foci with the transcriptomes of their parent fibroblasts, similar transcriptional changes were observed in both iPSCs and OF. A significant number of genes repressed during the formation of iPSCs were also repressed in OF, including a large group of genes associated with differentiation. In addition, both cell types showed increased metabolic activity – another evidence of the connection between these two cell types.
"We were surprised how similar iPSCs are to cancer–generating cells," Dr. Knepfler comments on the results. "Our findings suggest that the search for therapeutic applications of iPSCs should continue with great caution if we want to do everything possible to ensure patient safety."
Future experimental therapies using induced pluripotent stem cells will most likely not be associated with their direct implantation into the patient's body. Instead, iPSCs will be used to produce differentiated cells in the laboratory, which can then be used as transplants. This approach reduces the risk of developing tumors as a side effect. Nevertheless, Dr. Knepfler notes, even trace amounts of iPSCs can cause cancer in patients – a possibility confirmed by the latest research of his group.
It is encouraging that scientists have also found significant differences between iPSCs and OF, which may provide the key to making iPSCs more secure. As part of this study, the scientists transformed OF into iPS-like cells by changing their genetic composition (a process dependent on Nanog). Despite the fact that the behavior of reprogrammed cancer cells does not fully correspond to the behavior of iPSCs and they have less ability to differentiate into different cell types, these results are very interesting, as they demonstrate that cancer cells can be reprogrammed into more normal cell types, which may open the way to new cancer treatments.
"We have established that it is possible to reprogram cancer cells so that they behave almost like normal stem cells," Dr. Knepfler emphasizes. "This suggests that such reprogramming of cancer cells may become a new way of treating cancer patients, essentially forcing their tumors to transform into normal stem cells."
Knepfler's group continues to investigate the similarities and differences between induced pluripotent stem cells and cancer cells, and is also exploring possible ways to improve the safety of iPSCs. Apparently, targeting certain metabolic pathways may increase the effectiveness of obtaining iPSCs, while exposure to other pathways may increase their safety.
Portal "Eternal youth" http://vechnayamolodost.ru05.10.2012