Through the growth of cancer cells inside human tissue that developed in a mouse as a result of the differentiation of human embryonic stem cells, the researchers Dr. Mati Zuckerman and Prof. Karl Skortsky showed that cancer cells grow and multiply better in close proximity to human cells than in mouse tissue or in growth plates under laboratory conditions
Innovative research conducted at the Faculty of Medicine of the Technion and the Medical Research Center at Rambam Hospital may lead to the development of new research methods to control the development of cancerous tumors in humans and, among other things, to the transformation of cancer from a lethal disease to a chronic disease that can be controlled through medical treatment, similar to AIDS.
Using the growth of cancer cells inside human tissue that developed in a mouse as a result of the differentiation of human embryonic stem cells, researchers Dr. Mati Zuckerman and Prof. Karl Skortsky showed that cancer cells grow and multiply better in close proximity to human cells than in mouse tissue or in growth plates under laboratory conditions. The researchers also provide evidence for the great diversity of the types of cancer cells found in a single cancer tumor in a patient.
Dr. Mati Zuckerman, a senior researcher at the Rambam Medical College for Human Health, who leads the research project, states that the use of this model will facilitate the development of anti-cancer treatments that can destroy the malignant tumor cells, and in particular the cancer stem cells in the tumor, which are the ones that are more resistant to anti-cancer treatments -Cancerous and capable of replicating themselves and creating the tumor again. Previous studies have shown that cancer stem cells that have the ability to self-replicate are the ones that turn cancer into a lethal disease (a disease that kills people).
Prof. Skortsky of the Technion and Director of the Research Authority of the Medical College for Human Health - Rambam, points out that in this study there is an attempt to understand how a cancer develops and how it is actually possible to stop the uncontrolled growth of cancer cells.
In order to simulate as closely as possible the environmental conditions of a cancerous tumor in the patient's body, the researchers developed an innovative model system in which the malignant tumors develop within teratoma tissue that originates from the differentiation of human embryonic stem cells. Although this tissue is not organized into organs like the human body, it is composed of different types of normal cells, representatives of all tissues in the human body. The teratoma tissue that develops on the leg of the mouse is a platform for studying the development of malignant tumors and the proliferation of cancer cells.
For the research published in the prestigious journal STEM CELLS, the researchers used cancer cells taken from CLEAR CELL CARCINOMA ovarian cancer and grew them inside the teratoma tissue. Surprisingly, the cancer cells grew better in teratoma tissue than in mouse tissue in the mouse models used in this type of research. From a single tumor, from one patient, the scientists were able to isolate six subpopulations of cancer cells that differ from each other in their malignant potential, in their level of aggressiveness in the nature of the tumor they develop, and in the need of the malignant cells to recruit normal cells from the surrounding healthy tissue for help. These six subpopulations have clear characteristics of cancer stem cells, and in fact constitute an innovative finding that points to the variability that exists in the tumor already at the level of the cancer stem cells that develop the malignant tumor.
The complex of these properties, Dr. Zuckerman explains, is expressed in its entirety only when the cells grow in human tissue and the union of these different cells and their properties actually makes up the malignant tumor that was removed from the patient's body. The mouse models that are currently accepted for cancer research do not fully reflect the entirety of cancer cells and their properties as they are reflected in the innovative model, and above all the mouse tissue does not reflect the self-replicating properties of these cells as they are expressed in human tissue.
Prof. Skortsky states that he was not surprised by the effect of human tissue on the development of the malignant tumor, but was very surprised by the intensity of the effect (order of magnitude): "It is known that malignant tumors are actually complex organs, but I did not imagine that the effect of a cell environment that originates from the differentiation of embryonic stem cells on the development of a tumor Malignancy will be so powerful and will bring to light the significant role of the tissue in the process of tumor development."
The two researchers note that at this stage they are unable to specifically point out the factors that influence the growth of tumor development in human tissue and the research group, which also includes Sagi Abelson, Liron Berger and Ya'ala Shammai, invests a lot of effort in identifying and isolating the factors found in human cells that help to fully reflect the properties of different types Different types of cancer stem cells. It is possible that these factors, once identified, will allow modern medicine to treat cancer as a chronic disease: instead of treating the entire tumor, it will be possible to specifically identify and eliminate the mechanism that allows the cancer stem cells to replicate themselves and recreate the tumor.
In the next step, according to the researchers, ways must be identified and developed to block the factors that enable the self-replication of cancer stem cells so that they can be controlled through long-term anti-cancer treatments.
Funding for this research was done with the help of the National Science Foundation and the Daniel M. Soref Charitable Trust, the Skirball Foundation, the Richard D. Satell Foundation, the Sohnis and Forman families
