Deciphering a wave of cell death may in the future allow cancer tumors to shrink

Researchers from Ben-Gurion University have demonstrated for the first time, together with their colleagues from the Memorial Sloan Kettering Cancer Center in New York, how a 'wave of death' spreads between cells.  The discoveries are a basis for understanding the processes of planned cell death and for developing new treatments for cancer

Research conducted at Ben-Gurion University of the Negev allows a glimpse into one of the most fascinating processes in cellular biology - how does a cell commit suicide and lead to a chain reaction to the suicide of the other cells around it? Watch the documentation of the wave of death spreading between the cells, as captured by the researchers' camera.

Programmed cell death is a condition in which a cell destroys itself in a controlled manner as part of the normal functioning of the body. By developing a computational method for measuring cell death, the researchers characterized a new and intriguing intercellular communication mechanism that leads to the spread of death between cells in a way that enables the elimination of entire populations. The findings, published in the scientific journal Nature Cell Biology, may pave the way for the development of future cancer treatments.

The researchers followed the process under a microscope by introducing a fluorescent substance into the cell nucleus, which allowed the measurement of the expansion in space once the nucleus split as part of the cell's death process. The quantitative documentation of the death process in time and space can indicate a communication mechanism between the cells. The researchers identified a group behavior when the death process started with a cell that is sensitive to the treatment, and continues by "convincing" the cell next to it to commit suicide as well. This creates a chain reaction of cell death that can spread in the form of a wave.

Behind the study are researchers from Ben-Gurion University of the Negev and their colleagues from the Memorial Sloan Kettering Cancer Center in New York. The field of research of Dr. Assaf Zaritsky, a faculty member in the Department of Software and Information Systems Engineering at Ben-Gurion University of the Negev, deals with understanding complex processes in cells using diverse calculation methods. He teamed up with Prof. Michael Oberholzer from New York to investigate the spread of cell death in the group. The research was led by research student (now Dr.) Michelle Rigman from New York, with contributions from students Chen Gilad, Tom Levin and Liran Sagi from Ben-Gurion University.

Proptosis, a type of programmed cell death mechanism based on iron sensitivity, was only discovered about twenty years ago. In a preliminary study from 2016, the researchers from New York showed that the death mechanism can be activated to shrink cancerous tumors in mice, and suggested that the tumor shrinkage happens through the spread of death between cells. Now, in collaboration with the researchers from Ben-Gurion University, they have systematically demonstrated that the "death wave" is indeed a characteristic of proptosis under certain conditions. The discovery was made possible thanks to the development of image processing computational tools and the definition of quantitative indices under different experimental conditions. 

"The spread of death between cells may form the basis of cancer treatment, if we know how to activate the death signal in the middle of the tumor and make sure that it spreads only to the cancer cells, but not to healthy tissue," suggests Dr. Zaritsky. "When cancer is treated with radiation, it will be possible to see the effect of the treatment even in neighboring cells that were not exposed to radiation. This is an essential process in the fight against cancer," emphasizes Prof. Oberholzer.