Once cancer starts to spread to other parts of the body – a process called metastasis – it becomes much more difficult to treat. Now in a world first, an international study published in the journal Cell Reports and led by the University of Sydney in Australia identifies “bad” cholesterol as an important culprit in metastasis.
Cancer happens when normal cells start to behave abnormally, grow out of control and multiply to form lumps called tumors. If untreated, cancer cells can escape their primary tumors, travel to other parts of the body and grow into secondary cancers or metastases. Metastases are the major cause of death from cancer.
If we are to significantly improve cancer treatment, we need a better understanding of metastasis. One of the areas researchers are keenly investigating is what helps cancer cells escape primary tumors and set up new sites elsewhere in the body.
We already know that most of the cells in the body stick to each other because they have velcro-like molecules on their surfaces called integrins. In recent years, researchers have discovered that integrins help cancer cells to escape tumors and settle elsewhere in the body.
For instance, in 2012, Medical News Today learned of a study published in The Journal of Cell Biology that explained why migrating cancer cells often express integrins that provide better traction. The study revealed how a lipid-converting enzyme called DGK-Alpha helps cancer cells gain traction and mobilize.
So an important question in cancer research is how to block integrins so they stop cancer cells from moving and spreading. Some inhibitors of integrin have been developed, but they are not suitable for clinical use, say the researchers behind this new study.
‘Bad’ cholesterol helps integrins move, ‘good’ cholesterol keeps them inside cells
Researchers have discovered that integrins can move from the surface of cells to the inside, and thatcholesterol, one of the major lipids in the body, is needed to keep integrins on the surface of cancer cells. But the underlying mechanisms, until now, have been somewhat unclear.
Thomas Grewal, a senior author of this latest study and an associate professor in the Faculty of Pharmacy at Sydney, says they identified “that ‘bad’ (low density lipoprotein or LDL) cholesterol controls the trafficking of tiny vessels which also contain these integrins, and this has huge effects on the ability of cancer cells to move and spread throughout the body.”
He says they found high levels of “bad” cholesterol seem to help the integrins in cancer cells to move around, and in contrast, high levels of ‘good’ (high density lipoprotein or HDL) cholesterol seem to keep the integrins inside cells.
He and his colleagues conclude that fine-tuning of cholesterol levels could be a way to influence cancer cell migration and invasion.
Knowing “how to manipulate and lower ‘bad’ cholesterol could significantly help to reduce the ability of cancer cells to spread,” says Prof. Grewal, who with co-senior author Carlos Enrich, a professor in the Faculty of Medicine at the University of Barcelona in Spain, has been working on the link between cholesterol and cancer for 15 years.
Written by Catharine Paddock PhD