19 November 2018

In contrast to their non-metastatic counterparts, metastatic cancer cells show movement patterns that are also often employed by predators searching for prey. This was shown by an international study on movement patterns of cancer cells published in Nature Communications this month. Cell biologists from Radboud university medical center also participated in this study. The elimination of the ability of metastatic cells to execute such walks creates new opportunities to inhibit metastatic spread.

Nearly all living organisms show movement of one kind or another.  For instance, algae and bacteria appear to randomly jiggle about, whereas mammalians make targeted movements. A type of movement shown in many organisms is the so-called Lévy walk, which refers to minor diffusive movements interspersed with long excursions. This type of movement is not only characteristic of predators searching for scarce prey, but may also occur in people and even bacteria, individual immune cells and separate cell components. Such movement patterns have been found in cancer cells as well.  

Microtracks

An international research team led by the Ulsan National Institute of Science and Technology in South Korea has studied the function of Lévy-like movement patterns in cancer cells. The team used microscopic slides in which microtracks had been etched. The width of these tracks was sufficient for one cell to freely move from left to right (video). The researchers studied the movements of both non-metastatic and metastatic breast, skin and prostate cancer cells. Only metastatic cells displayed movement patterns consistent with Lévy walks, i.e. an initial long excursion to the left or right, followed by a number of small steps back and forth, again followed by a long excursion. These patterns were not found in non-metastatic cells, which only made diffusive movements. 

Long excursion and small steps

The Lévy movement vaguely resembles the actions taken when searching for lost keys. Initially, you look closely at a particular spot, for instance your purse. Next, you leap toward another spot, e.g. the kitchen drawer, now closely searching this spot. This change between major targeted leaps and minor movements is typical of the Lévy walk. In the wild, e.g. when predators are searching for prey,  this turns out to be a favorable approach with an optimal balance between effort and search results. 

3D collagen model

Although linear microtracks are found in living tissues, for instance along muscle fibers or collagen bundles, most tissues have a more complex three-dimensional structure. Therefore, researchers from Radboud university medical center studied the behavior of cancer cells by using a 3D collagen model. In this model, too, Lévy-like movement patterns were found in metastatic cancer cells. Although this 3D model is a better representation of the real-life situation, it does not take into account environmental factors. To measure the impact of these environmental factors on cell movements, the behavior of cancer cells was then studied in living tumors.

Mouse

The researchers from Radboud university medical center studied both non-metastatic and metastatic melanoma cells in the skin of a mouse. Both types of cells were shown to spread by forcing hair-like dendrites into spaces between collagen, blood vessels, nerves and muscle cells. In this case, too, only metastatic cancer cells showed movements consistent with Lévy walks (video). These cells moved faster and more targetedly without being influenced by environmental factors. Apparently, this is the optimal movement strategy for cancer cells to quickly and targetedly find suitable loci to seed metastatic cancers.  

Weak spot

As the predatory movement appears to be an intrinsic property of metastatic cancer cells, it may be interesting to eliminate this ability. By doing so, tumor cells may be prevented from making predatory movements. As a result, metastatic spread may also be prevented. The researchers inhibited two proteins which need to collaborate in order for a cell to move in a targeted manner. Without these collaborating proteins, the Lévy walk was reverted into regular diffusive motions characterizing benign, non-metastatic cancer cells. Therefore, the Lévy walk could be the weak spot of cancer cells.
 

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