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Fig. 4.4
Photomicrographs showing in vivo MDA-MB-435s tumor cell adhesion to a single
perfused microvessel under control with 1%BSA Ringer perfusate and under treatment with
1 nM VEGF perfusate after (
a
) ~15 min and (
b
) ~60 min perfusion. The perfusion velocity is
~1,000
m/s, which is the mean normal flow velocity in post-capillary venules. Bright spots
indicate adherent tumor cells labeled with fluorescence. From Shen et al. [
69
]
m
4.4.3
Integrin Signaling, Cell Adhesion Molecules,
and Tumor Metastasis
Although the nonspecific trapping due to the friction between the tumor cells and
the narrow part of microvasculature is found to be responsible for the initial tumor
cell arrest [
34
,
37
,
43
,
54
], the cell adhesion molecules are required for the adhesion
in larger microvessels and transmigration [
12
,
24
,
34
-
36
,
41
,
45
,
49
,
69
-
71
,
73
].
The integrins are a family of signaling and cell adhesion receptors, which attach
cells to the extracellular matrix (ECM) and in some cases to other cells, and
cooperate with growth factor and cytokine receptors to regulate cell behavior.
Signals elicited by integrins enable tumor cells to survive, proliferate, and migrate
independently of positional constraints [
38
], and adhere [
24
]. The
4 integrin is a
laminin-5 receptor and was originally described as a “tumor-specific” protein,
a
6
b
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