Different Morphologies of Tumor Invasion Fronts - Cellular Potts Models: Multiscale Extensions and Biological Applications - page 144

crombie to describe the influence on cell crawling of the contact interactions
between individuals [1]). The rest of the population remains instead relatively
compact, with only some cells wade just outside the body of the tumor, see
light-bordered region in panels (A) and (B) of Figure 8.4. The migratory and
invasive capacity of such \internal" individuals is in fact inhibited by both
the limited access to chemicals and by the high cellular density, which enforce
cell{cell adhesive interactions. As shown in Figure 8.4(C-D), at the end of the
invasive phase, the host tissue is significantly modified, as the matrix proteins
have been dramatically degraded (notice in the same figure the paths of pro-
tein gradients which drive cell migration) and the growth factors have been
significantly consumed.

8.4 Varying Cell Adhesive Properties
As widely commented in the previous sections, the values of the parameters
J ext s have a clear biological relevance, as they describe the relative prefer-
ence of tumor cells to be in contact with other cells or with the extracellular
medium. At a molecular level, they are therefore a measure of the expression
and the engagement of the different types of cell adhesion molecules, cadherins
and integrins, respectively. Indeed, the variation of the J ext is is expected to
have a substantial impact on the overall invasiveness of the disease.
We rst change the cell{cell adhesive strength J ext

T;T ; see Figure 8.5. At low

values of the parameter (i.e., J ext

T;T < J ext

T;M , which means higher cell{cell ad-
hesiveness), the tumor remains compact, with the highly motile external cells
that clump along the front of the mass, rather than invading significantly
the surrounding tissue; see Figure 8.5(A). This phenomenology is due to the
fact that the cell-cell adhesive interactions are too strong to be overcome by
the other forces experienced by malignant individuals and therefore stabilize
tumor morphology. At large values of J ext

T;T , the tumor instead expands and in-
vades deeper: the external cells quickly spread away from the rest of the mass
creating a dispersed front (fewer of them are in contact with each other within
12 h) and a repulsion occurs also among individuals within the main body of
the mass. The subsequent formation of islands of free matrix within the center
of the tumor, which are then only partially filled in again, increases the overall
bias toward invasion, as reproduced in Figure 8.5(B). From these results, we
can conrm that an alteration in cell{cell adhesive properties is an impor-
tant consideration in determining the severity of the disease. In particular, a
biomedical intervention that is able to enforce cell{cell adhesive interactions
allows to control the morphology of the lesion which, remaining smooth and
densely packed, can be more easily treated surgically. The presented compu-
tational outcomes are consistent with a number of in vitro experiments: for