Biomedical Engineering Reference
In-Depth Information
In the cellular automaton, a layered tumor has formed, comprised of
necrotic \cell" material, quiescent and proliferating tumor cells.
8. Capsule is a key prognostic indicator
The formation of a capsule of dense, brous extracellular matrix around a
solid tumor is a key prognostic indicator in a wide range of cancers. How-
ever, the cellular mechanisms underlying capsule formation remain unclear.
The dormant state is ended by invasion into surrounding tissue. Tumor
encapsulation is the cascade of events that result in the formation of a
multi-layered sheath of epithelium surrounding a tumor. A multilobular
tumor is one in which lobes of dierent sizes are separated by strands of
connective tissue.
8.1. Capsule composition and importance
Two complementary theories have been postulated in order to explain the
mechanism of capsule formation
7;8
. One hypothesized mechanism is the ex-
pansive growth hypothesis, which suggests that a capsule may form by the
rearrangement of existing extracellular matrix without new matrix produc-
tion. Berenblum
11
observed that tumors growing within the lumen of a
hollow organ, or on the surface of the body, do not become encapsulated, a
nding that Berenblum suggests conrms the hypothesis that capsules can
only be formed in situations where a tumor can exert pressure on surround-
ing tissue. According to the expansive growth hypothesis, the appearance
of brous capsule is essentially a passive phenomena, and the capsular col-
lagen is derived from mature, pre-existing collagen rather than being newly
deposited. The aggregation of connective tissue represents the cumulative
eect of a series of lower level interactions at the interface of the expanding
tumor and the connective tissue. The implication of this hypothesis was
proposed studied by Perumpanani at el
60
. The macrocellular scale model
consists of conservation equations for tumor cells and extracellular matrix
and exhibit traveling wave solutions in which a pulse of extracellular ma-
trix, corresponding to a capsule, moves in parallel with the advancing front
of the tumor. Their model consists of conservation equations for the den-
sities of tumor cells and extracellular matrix, denoted u(x; t) and c(x; t),
respectively, where t and x denote time and space in a one-dimensional
spatial domain:
@u
@t
@
@x
h(c)
@u
@x
= f(u) +
;
(4)
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