It’s not only strength, direction also counts in cancer cell invasion

To metastasize, cancer cells “muscle” their way through tissue, but some highly metastatic cells make particularly efficient use of force. 

 

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We, together with Jim Butler from Harvard University, have developed a method to measure the energy that a single cancer cell generates during migration through a dense 3-dimensional connective tissue matrix with pores that are much smaller than the cell body. We found that, as expected, weak cancer cells remain immobile, but surprisingly, so do some of the strongest cells.  Only when cells focus their forces in a certain direction can they invade tissue. This observation has now been published in the journal PLoS ONE (http://dx.plos.org/10.1371/journal.pone.0033476).

The search for a universal marker that can distinguish aggressively invasive and metastatic cells from less invasive cancer cells has so far been elusive, yet it is generally assumed that large forces generated by the metastatic cells help them to move through the small pores of connective tissue.  This study now demonstrates that large forces are not sufficient.  To invade, cancer cells need to align the forces in a preferred direction, and they do so by changing their cell shape.  Accordingly, elongated spindle-like cells invade dense tissue particularly efficiently. It is currently unclear if force magnitude and alignment can be selectively reduced in cancer cells, but if a way is found, this may open up new therapeutic strategies against cancer.