VANDERBILT UNIVERSITY; BEGUM ERDOGAN, DONNA WEBB
Fibroblasts, cells that produce and organize the extracellular matrix (ECM) appear to be in cahoots with metastasizing tumor cells, according to research presented at the annual meeting of the American Society for Cell Biology (ASCB) in San Diego this week. Scientists have long suspected that fibroblasts serve as cancer’s assistants as it spreads throughout the body, dubbing the cells cancer-associated fibroblasts (CAFs); now, Donna Webb of Vanderbilt University and her colleagues have shown that CAFs “clear a highway through the ECM for migrating cancer cells,” according to a press release.
This highway is made of fibronectin, an ECM protein secreted by fibroblasts. Using confocal imaging, the Vanderbilt team watched as CAFs rearranged fibronectin into parallel bundles, rather than the dense mesh typically found in the ECM. Plating cancer cells on ECM grown from CAFs or from normal fibroblasts, the researchers saw that the cancer cells were able to move more easily along the tracks laid by the CAFs. The group further found differences between CAFs and normal fibroblasts in the activation of the GTPase Rac, which is known to be involved in cell movement, and in how the cells delivered force from the motor protein myosin II. Inhibiting myosin II activity destroyed the parallel fibronectin highway, replacing it with the normally disarrayed ECM.