The discovery of the cell, which they are calling ‘the cell of origin’ sheds new light on what fuels cancer growth and how to potentially stop it.
Lead researcher Professor Michael P Lisanti said: “If, as we believe, we have found the beginning of the road, we may have to press the reset button on how we treat cancer with drugs.”
Describing the cell and its functions in the Journal Frontiers in Oncology, the team from the Biomedical Research Centre at the University of Salford say the findings “rewrite what we know about the process of cancer growth” and offer new evidence that cancer stem cells are highly proliferative and driven by mitochondrial function.
“Scientists talk about cancer being caused by dying cells coming back to life, so-called ‘zombie-cells,” explains Lisanti.
“We now see it is more dramatic than that. In fact, it could be more accurately described as a prison break.
“In other words, this origin cell breaks out of line and runs amok, multiplying malignant cells and creating a tumor.”
Using auto-florescence techniques, the Salford team, which included Federica Sotgia and Marco Fiorillo, isolated the most energetic cells in a series of cell lines of cancer cells derived from human breast tumors.
They found that of the most dynamic cancer stem cells, representing 0.2% of the cell population, had special characteristics, with significantly more energy than average cancer cells.
They then cross-checked the cell’s ‘performance’ in terms of mitochondrial hyperfunction, rate of proliferation and a factor they call ‘stemness’ – in other words if it is capable of creating a tumor.
They also found the cells displayed characteristics of senescence with one biomarker of senescent namely p21-WAF, increased by ~17-fold in these cancer stem cells.
“If we ask where do these cells come from, the evidence indicates they emerge from senescent (dying) cells,” said Professor Sotgia.
“They displayed hallmarks of senescence but are no longer senescent, they have broken out of senescence.”
The explanation for this appears to be in how the cells become re-energized. They may have used anti-oxidants and mitochondrial energy, to release themselves and so reverse cell cycle arrest.
Added Lisanti: “It feels like finding the proverbial needle in a haystack, and it crucially gives us a new window on cancer and how we might stop it.
“Most cancer patients die because of the spread of tumor cells to distant sites, known as metastasis.
“The evidence is increasingly that metastatic cancer stem cells, fuelled by mitochondria, are responsible. Yet, most chemotherapy targets the bulk cancer cells. Some chemotherapy even makes cancer stem cells proliferate more.”