How a cancer cell migrates across a 2D surface says little about its ability to move through a 3D matrix, Meyer et al. reveal, but measuring membrane protrusion can be much more informative.
A metastasizing tumor cell moves through 3D tissues, yet, largely because they're easier to perform, most studies of cell migration are carried out on 2D surfaces. Meyer et al. wanted to investigate how well 2D assays replicate 3D motility and to determine what parameters best predict a cell's migration through 3D environments.
The researchers tracked the migration of several breast cancer cell lines on a variety of 2D and 3D matrices in response to different growth factors associated with metastasis. The speed and directional persistence of the cells’ movements on 2D surfaces bore little resemblance to their behavior in 3D matrices. And, although a cell's migratory response to different growth factors could be partially predicted by measuring which growth factor receptors it expressed, differences in receptor expression and activation levels couldn't account for all the variation seen in different cell lines.
Meyer et al. then examined whether any individual steps of 2D migration correlated with 3D motility and found that the extent to which cells formed membrane protrusions in response to different growth factors was a reliable predictor of their 3D migratory behavior. Strengthening the connection, cytoskeletal inhibitors that preferentially block 3D migration also impeded membrane protrusion in 2D. The authors now want to develop high-throughput methods for measuring membrane protrusion in order to facilitate screens for drugs and siRNAs that affect 3D cell migration.