Biomedical Engineering Reference
In-Depth Information
overall invasion is partially discouraged. The phenomenon of \ngering" has
been captured by other discrete models [370, 395], and characterizes many
malignancies (see for example Figure 8.10). In particular, recent studies of
photo-micrograph have shown that the \ragged" surfaces of dierent tumors
contains fractal components at the smaller, cellular scale, that relate to the
overall severity of the disease [96, 227]. However, tumors with an unstable fin-
gered morphology are typically more aggressive and hard to be treated than
smoother ones: in fact, even if their invasive depth is limited, they are dicult
to be surgically removed.
We nally characterize the tumor patterns emerging for dierent cell{cell
adhesive interactions (i.e., given by parameter J
ext
T;T
) in the case of either non-
proliferative or proliferative individuals. The obtained results are graphically
summarized in Figure 8.11. At high intercellular adhesiveness, the cancerous
mass remains compact and smooth: indeed, its invasive distance is specifically
determined by the mitotic rate of malignant individuals. On the opposite, at
low cell{cell adhesion, the tumor invades the surrounding environments with
a front of dispersed aggressive individuals, with islands of free tissue forming
within the main mass. Also in this case, cell replication enhances the invasive
potential of the cancer, leading to the most aggressive disease, which deeply
penetrates in the surrounding tissue with an increasing number of scattered in-
dividuals. Finally, at intermediate values of intercellular adhesive connections,
we observe the formation of a ragged tumor front only in the case of prolif-
erative individuals: this suggests that fingers of malignant cells can emerge
only with a specific balance between their mitotic potential and their adhe-
sive strength. Reviewing the results in Figure 8.11, we can therefore conclude
that tumor patters are primarily differentiated by the variation of the cell
adhesive potential, while the invasive depth is definitively dependent from the
cell mitotic rate. Of particular interest is the unstable fingered morphology
characterizing a small region of the cell biophysical parameter space.
8.8 Early Stages of Tumor Spheroid Growth
During the first period of avascular growth (or when cultured in vitro in a
three-dimensional gel, as studied in Chapter 3), a primary tumor may also
organize in a sphere-like hyper-proliferative colony, which has to rely upon
the host for crucial substances, such as oxygen, nutrients, and growth factors
[7, 275, 401]. Substrate gradients therefore form within the growing cancer
mass, causing a well-localized phenotypic specification of malignant individ-
uals, which typically differentiate in an outer viable rim of highly metabolic
and proliferative cells, an interior band of quiescent individuals and a central
necrotic core, formed by cells dead for deprivation of vital chemicals [47]. In
particular, in this stage, the increment in cell mass due to the aberrant mito-
Search WWH ::
Custom Search