Discovery of 'cell projection pumping' presents new cancer target
A novel finding by a team of University of Sydney researchers has revealed a new source of cancer cell diversity, which could have profound implications for cancer treatment.
Although most cancer cells are killed by chemotherapy, diversity among individual cells means they vary in their sensitivity to treatment, enabling some cells to survive.
Previously, it was thought to be mostly due to genetic variability among cancer cells, but new research from Professor Hans Zoellner and a team of researchers from the University of Sydney School of Dentistry has uncovered a whole new source of diversity.
In 2012, Professor Hans Zoellner led a team to discover that cancer cells exchange contents with surrounding normal cells (called fibroblasts), but the mechanism remained unknown.
The latest discovery by Zoellner's team, published in Biophysical Journal finally explains how - presenting a new oncologic drug target, according to the researchers.
How cell-projection probing causes cancer cell diversity
All cells constantly probe each other with tentacle-like cell-projections. These reach out to neighbours, probe, and then retract, as part of the way cells sense their environment.
When a cell-projection retracts, there is a brief increase in fluid pressure within the projection, to force cytoplasm – the jelly-like fluid within the cells – back into the cell body.
Studying cells in time-lapse movies, Professor Zoellner noticed that transfer results from retracting cell-projections.
Diagram of Cell-Projection Pumping and Explanation
He reasoned that transient micro-fusions between the retracting cell-projections and any neighbouring cell, would permit cytoplasm from the cell-projection to be injected into the neighbour, instead of being returned to the fibroblast.
His team tested this idea by combining mathematical modelling, cell experimentation, and computer simulation. The outcome, a discovery of what seems a previously unknown biological mechanism, now coined ‘cell-projection pumping’
The significance of the finding is underscored by separate work published by Professor Zoellner’s team in collaboration the Memorial Sloan-Kettering Cancer Center, which shows cancer cells become more diverse in size and shape and more aggressive after cell-projection pumping.
"This is a whole new cancer target. Now that we know it’s happening, we can think about trying to block it, and work towards better outcomes," said Zoellner.
Professor Hans Zoellner is the Head of Discipline or Oral Pathology at the University of Sydney and is currently leading ongoing projects in cell-projection pumping; bone remodelling, albumin anti-apoptotic activity, and dental robotics.