Thus, migration speed is a function of the strength of attachment and is maximized when migrating cells can cycle their adhesions ( 13, 14). For optimal cell migration into adjacent parenchyma, cells must turnover their focal adhesions (FA) to move through the tissue effectively extremely unstable or stable adhesion can arrest migration as the cell can never establish contractile forces or unbind and retract rear portions of the cell ( 13). Given that all cancer cells must interact with the ECM to initiate metastasis, understanding variations in these interactions can serve as an early indicator of metastatic ability. Assays based on these metrics focus largely on characterizing the physical properties of already circulating cells rather than understanding how cancer cells physically interact with and adhere to the extracellular matrix (ECM) at the onset of invasion. These data suggest that adhesion strength could potentially serve as a stable marker for migration and metastatic potential within a given tumor population and that the fraction of weakly adherent cells present within a tumor could act as a physical marker for metastatic potential.īiophysical markers, such as cell deformability, are an emerging alternative to assess metastatic potential ( 7–12). In human breast tumors, expression of genes associated with the weakly adherent population resulted in worse progression-free and disease-free intervals.

Subpopulations did not show differences in expression of proteins involved in the focal adhesion complex but did exhibit intrinsic focal adhesion assembly as well as contractile differences that resulted from differential expression of genes involved in microtubules, cytoskeleton linkages, and motor activity.

Weakly adherent cells displayed increased migration in both two-dimensional and three-dimensional migration assays this was maintained for several days in culture. Adhesion strength is heterogeneous even among cancer cells within a given population, and using a parallel plate flow chamber, we separated and sorted these populations into weakly and strongly adherent groups when cultured under stromal conditions, this adhesion phenotype was stable over multiple days, sorting cycles, and common across all epithelial tumor lines investigated. Common to disseminating cells from such tumors, however, is the need to modulate their adhesion as they detach from the tumor and migrate through stroma to intravasate. Despite significant effort, there is no universal biological marker that serves as a metric for metastatic potential of solid tumors. Tumors are heterogeneous and composed of cells with different dissemination abilities.

How to test adhesion gel in portal 2