Different Morphologies of Tumor Invasion Fronts - Cellular Potts Models: Multiscale Extensions and Biological Applications - page 162

FIGURE 8.17: 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). By enforcing cell{cell adhesion, the
spheroid remains densely compact and smooth with a low invasive potential.
On the contrary, decrements in cell{cell adhesion lead to increments in the
malignancy of the lesion, as external cells quickly shed in the host tissue and,
consequently, also internal individuals have access to vital growth factors,
surviving and proliferating. Examples of final configurations for J C;C = 0:5
(left panel), J C;C = 4:5 (central panel), and J C;C = 7:5 (right panel).
These results represent a denitive conrmation that an alteration in cell{
cell adhesive properties is an important consideration in regulating the mor-
phology of the disease and, eventually, in determining its severity. As a sup-
port of the model outcomes, a number of experimental studies have recently
demonstrated that the downregulation of cadherin molecules is implicated in
a variety of metastatic cancers [71, 72, 83, 385]. In particular, glioma cell lines
with low N-cadherin expressions have been observed to aggressively invade
matrix gels, whereas the same populations with a high N-cadherin activity
have been instead shown to grow slower and to expand less significantly in
the host tissues [205, 182].