New research could help combat spread of cancer, scientists say
Spreading cancer can be halted by blocking a key mechanism that allows tumour cells to break free from their birthplace, research has shown.
Cancer cells move using large structures called focal adhesions that act like rolling "tank tracks" to propel them forward.
To avoid getting stuck, the adhesions must be removed once they pass from the front to the back of the cell.
This is done by means of a self-devouring process called autophagy that breaks the structures down, scientists have discovered. By suppressing autophagy, they were able to anchor tumours in one place and prevent cancer cells from spreading.
The research could pave the way for ground-breaking treatments that combat metastasis, the lethal transmission of cancer from a primary tumour location to other parts of the body such as the liver, lungs, brain or bones.
Dr Kay MacLeod, from the University of Chicago, said: "Using genetic and chemical means, we showed that autophagy is required for the motility and invasion of highly metastatic tumour cells.
"Our work suggests that inhibiting autophagy in the clinical setting may be an effective approach to block metastatic dissemination."
Metastasis is responsible for 90% of all cancer deaths. Without it, cancers would find it harder to survive, since tightly packed, rapidly growing tumours quickly exhaust their available supplies of oxygen and nutrients.
By migrating away from the original tumour, cancer cells are able to establish themselves in less crowded environments where they have room to breathe and flourish.
Using time-lapse microscopy, the researchers monitored active metastatic breast cancer cells moving around in a laboratory dish.
But after the team knocked out two autophagy-related genes, the cells ground to a complete halt.
"They appeared to be stuck", said Dr MacLeod.
When the genetically modified cancer cells were injected into female mice, they formed primary breast tumours but failed to metastasise to other body sites.
A closer look revealed that the cells' focal adhesions were more numerous than usual, and abnormally large.
With their autophagy system switched off, the cells were unable to clear away unwanted focal adhesions which remained in place, growing larger and larger.
Dr MacLeod said: "Through the microscope, you can see the cell wobbling, trying to move, to put out new protrusions, to migrate. But it can't, because it is stuck, unable to dissolve the adhesions at the back end of the cell.
"Basically, autophagy-deficient tumour cells cannot migrate and as a result cannot travel to another location. This is why we think that inhibiting autophagy could block tumour metastasis."
The researchers observed a similar phenomenon in metastatic melanoma skin cancer cells, suggesting that other types of cancer also relied on autophagy to spread.
Several already approved drugs have the ability to disrupt autophagy, said the scientists, whose work is published in the journal Cell Reports.
They include the anti-malaria drug hydroxychloroquine which is currently being tested in clinical trials as a way to slow tumour growth.
However, it is not being investigated as a treatment specifically targeting metastasis.
"We would like to see trials designed to evaluate the efficacy of hydroxychloroquine or related drugs at blocking the progression to metastasis," said Dr MacLeod. "We think that's where this approach of inhibiting autophagy will be most useful as an anti-cancer measure."