In collaboration with the University of Tokyo, a research group led by Professor Ryouichi Horie, Faculty of Health Sciences, Kitasato University, has successfully shown that in Hodgkin lymphoma (HL), the differentiation of cancer cells is controlled by the interaction of reactive oxygen species (ROS) and hypoxia-inducible factors (HIF-1α) in cells.
Cancer has traditionally been considered a collection of homogeneous cell populations. Recent studies have revealed that cancer cells comprise a heterogeneous population of cells differentiated from cancer stem cells; however, the differentiation control mechanism of cancer cells remains unknown. Why are cancer cells able to persist in the body? This simple question served as the starting point for the group’s research.
"Cancer cells consist of the original stem cells and diverse populations that differentiate from them," Dr. Horie said. "In order to understand cancer cells, it was important to understand the mechanisms of this differentiation." The research group used an HL cell line as a model, in which the differentiation of cancer cells was observed morphologically. Research was conducted to clarify the differentiation control mechanism of cancer cells. The research group identified undifferentiated and differentiated cell populations using flow cytometry (a method that shines a laser light on cells and detects scattered light to observe the properties of individual cells) and observed an increase in intracellular ROS levels in differentiated cell populations compared with those in undifferentiated ones.
Differentiation was induced in the HL cell line by hydrogen peroxide, a type of ROS. In the undifferentiated cell population of the HL cell line, hypoxia-related gene expression was increased, and this population was in a hypoxic condition compared with differentiated cells. When the group focused on the hypoxia-induced transcription factor HIF-1α, strong HIF-1α expression in undifferentiated cells compared to differentiated cells was observed, and further examination showed that HIF-1α induced heme oxygenase-1 (HO-1: a protein whose expression is induced by inflammatory cytokines) involved in ROS degradation to suppress cell differentiation.
"In this study, we were able to use an experimental system that allows us to ascertain the differentiation of cancer cells by examining their morphology," Professor Horie said. "In the future, we would like to investigate the possibility of depleting cancer cells in the body by focusing on the molecular groups that control the differentiation of cancer cells, for example, by forcing the process of differentiation. As a clinician in hematology, I would like to contribute more broadly to the development of new therapies through research."
This article has been translated by JST with permission from The Science News Ltd.(https://sci-news.co.jp/). Unauthorized reproduction of the article and photographs is prohibited.