A research team of the Faculty of Science and Medicine of the University of Fribourg has shown that breast cancers comprise not one, but two distinct groups of stem cells – an important discovery for the better understanding of the cellular heterogeneity of these tumours and how they proliferate.
Dr Albert Santamaria-Martínez and his team used two different identification strategies to indicate the existence of these two populations of cancer stem cells (CSC) and so cast light on mechanisms of primary importance in the field of cancer biology. In point of fact, cancer stem cells are at the top of the tumour hierarchy. They are the root cause of both primary tumours and their metastases which cause 90% of deaths due to the cancer. They are also responsible for relapses. These cells typically represent only a very small fraction of the tumour, but they are resistant to classic chemotherapy.
Less metastases, more primary tumours
To understand the heterogeneity of the CSC pool, the researchers of the University of Fribourg used a model of animal experimentation using mice. In this way they were able to observe that the tumours contain two populations of cancer stem cells. The first group are readily able to regenerate primary tumours following transplantation, while the second easily regenerates secondary tumours, but not primary ones. In order to understand how these cell populations are regulated, Flavia Fico, lead author of the study, used pharmacological and genetic modelling of a biological process known as epithelial-mesenchymal transition (EMT) which is necessary for the formation of metastases. She observed that the inhibition of epithelial-mesenchymal transition hinders the formation of metastases, but produces CSCs having an increased potential to regenerate primary tumours more resistant to certain chemotherapeutic agents.
So these results potentially have important implications for breast cancer patients, since EMT inhibitors are currently being clinically trialled.
The results of this study have been published in Stem Cell Reports under the title: «Breast Cancer Stem Cells with Tumor- versus Metastasis-Initiating Capacities Are Modulated by TGFBR1 Inhibition».