Vanderbilt researchers show how metastasising tumours use non-cancerous fibroblasts to make a migration highway through surrounding extracellular matrix.
To get moving, metastasising cancer needs to enlist non-cancerous collaborators.
Suspicions about where these secret cancer allies might be lurking have long been directed at the fibroblasts, the cells that secrete and organise the extracellular matrix (ECM), the ground on which surrounding cells can get a grip.
Increasing evidence suggests that fibroblasts near growing tumours are actively assisting cancer cells in spreading locally and metastasising elsewhere.
But exactly how these cancer-associated fibroblasts (CAFs) provide aid to the cancer enemy was not known until a recent discovery by Begum Erdogan and colleagues in Donna Webb's lab at Vanderbilt University--CAFs clear a highway through the ECM for migrating cancer cells.
The roadway that CAFs arrange is made of parallel fibers of fibronectin (Fn), a major protein in the ECM mix secreted by all fibroblasts.
The Vanderbilt researchers observed CAFs rearranging Fn into parallel bundles instead of the dense mesh that normal tissue fibroblasts (NAFs) make.
Taking cancer cells grown from prostate as well as head and neck tumours, the researchers plated them on ECM from CAFs and NAFs.
The cancer cells on the CAF matrix were better at moving in a single direction.
But why?
CAFs rearrange the matrix into a road because they get a better grip on Fn fibers, the researchers discovered.
Using traction force microscopy, they were able to measure the difference.
CAFs were stronger than NAFs because they were better at delivering force from the motor protein, myosin II, through connectors called integrins to Fn fibers.
CAFs had higher levels of a Fn-binding integrin plus a switched-on GTPase called Rac, which is critical to cell movement.
Inhibiting myosin-II activity with a drug deprived CAFs of their super traction powers and the ECM reverted to its normal disorder.
These results solve a longstanding puzzle about cancer metastasis and point to the matrix as a possible target for drugs to stop cancer in its tracks.
We are an independent charity and are not backed by a large company or society. We raise every penny ourselves to improve the standards of cancer care through education. You can help us continue our work to address inequalities in cancer care by making a donation.
Any donation, however small, contributes directly towards the costs of creating and sharing free oncology education.
Together we can get better outcomes for patients by tackling global inequalities in access to the results of cancer research.
Thank you for your support.