Different Morphologies of Tumor Invasion Fronts - Cellular Potts Models: Multiscale Extensions and Biological Applications - page 161

FIGURE 8.16: Invasiveness of the tumor mass in response to alterations
of cell{cell adhesive strength, J C;C (i.e., all the other model parameters are
the same as in the simulation in Figure 8.13). Regression of the final depth
of invasion d(t = 15 days) vs J C;C . Downregulations of intercellular contact
interactions enhance the invasive potential of the tumor.
overexpressions of intercellular adhesive molecules, the final invasive radius
of the spheroid slightly decreases. In particular, the tumor remains compact
and strictly packed, without single individuals shed in the surrounding tissue,
see left panel of Figure 8.17. An enhanced activity of cadherins in fact is
able to stabilize the morphology of the disease, reducing its aggressiveness: a
smoother carcinoma mass can be in fact more eciently treated surgically.
As J C;C starts to increase, the tumor expands and invades deeper. The
progressive reduction of cell-cell adhesive interactions results in fact in an
increasing number of single individuals able to escape from the main mass
into the external environment (see also central panel of Figure 8.17).
Finally, at even large values of J C;C (i.e., > J C;M ), not only the external
cells quickly loose contact, dissociate and spread away from the rest of the
mass creating a dispersed ring (fewer of them adhere with each other within
2 days, not shown), but a repulsion occurs also among individuals within
the core of the mass. The surface area of the tumor/host interface therefore
increases, thereby allowing internal cells greater access to vital growth factors
needed to survive and eventually to proliferate. The overall tumor is therefore
able to overcome the diffusional limitations and continues to expand both in
the number of cells and in their dispersion, which further increases the overall
bias toward invasion, as reproduced in the right panel of Figure 8.17.
Interestingly, there is not a critical value of the cell homotypic adhesion
that clearly separates a compact phenotype of the tumor from a scattered
configuration: rather the metastatic potential of the disease increases progres-
sively with the downregulation of cell{cell contact strength.