Biomedical Engineering Reference
In-Depth Information
FIGURE 8.6: Invasiveness of the tumor mass in response to alterations of
cell{matrix adhesive strength, J
ext
T;M
(i.e., all the other model parameters are
the same as the simulation in Figure 8.4). Decrements in cell{matrix adhesive
interactions discourage the aggressive behavior of the lesion. In particular, for
high J
ext
T;M
> J
ext
T;T
, the malignant cells remain closely packed each other. (A)
Final configuration for J
ext
T;M
= 8:5. (B) Final depth of invasion d
f
vs. J
ext
T;M
.
The error bars show standard deviation over 10 realizations.
example glioma cell lines with a high N-cadherin expression have been seen
to invade less significantly different types of collagenous matrices [182].
We next vary J
ext
T;M
. The decrement of J
ext
T;M
has a relatively subtle effect
on the malignancy of the tumor, as its invasive distance does not dramatically
change (see Figure 8.6(B)). This is due to the fact that tumor cells prefer to
adhere to extracellular matrix elements already with the standard parameter
setting, (i.e., J
ext
T;M
< J
ext
T;T
, see Appendix C). At high values of J
ext
T;M
(i.e.,
J
ext
T;M
> J
ext
T;T
, which means a lower cell{matrix adhesiveness) the invasion is
instead strongly discouraged, as also the cells at the front remain close to
the body of the mass, with occasional individuals shed in the extracellular
environment (see Figure 8.6(A)). The cancerous cells are in fact simulated to
have an underexpression of integrin molecules: the haptotactic force alone is
unable to balance the cell{cell adhesive interactions and therefore to cause the
scatter of individuals. These considerations suggest that the use of drugs that
interfere with cell{matrix adhesive interactions, either by altering the amount
of ligand in the matrix or by inhibiting integrin molecules (which, as seen, are
overexpressed in tumors), has the potential to limit malignant invasion, and
eventually, to render the cancer more partial to resection.
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