Biomedical Engineering Reference
In-Depth Information
adhesion molecules, highlighting clinical data and i ndings from
in vivo
and
in vitro
experiments.
ROLE AT THE PRIMARY TUMOR SITE
Tumor cells secrete many inl ammatory factors, which lead to increased leukocyte
recruitment. Cancer progression is af ected by the ini ltrating immune cells. Over
the years, it has become clear that immune cells can function in both anti- and
pro-tumorigenic roles. Myeloid-derived suppressor cells and T regulatory cells,
through their ability to suppress immune function, augment tumor progression.
Ini ltrating myeloid cells can secrete factors that enhance angiogenesis and
promote tumor growth. In contrast, some ini ltrating immune cells kill the tumor
cells, acting in an anti-tumorigenic fashion. h e endothelium in and around the
tumor is important in the recruitment process.
As with other inl ammatory reactions, inl ammatory factors secreted by
the tumor, such as interleukin 1 beta (IL-1β) and tumor necrosis factor alpha
(TNF-α), increase adhesion molecule expression on the endothelium leading to an
activated state (Tedder
et al.
1995, Goldsby
et al.
2003, Castermans and Grii oen
2007, Dittmer
et al.
2008, Brooks
et al.
2009). Circulating leukocytes adhere to
this activated endothelium and, using the rolling mechanism described above,
move into the tumor (Castermans and Grii oen 2007). As leukocyte-endothelial
interactions are described in detail in a previous chapter, our main focus will be
the role of endothelial cell adhesion molecules in metastasis.
ROLE IN METASTASIS
Many cancers have been shown to metastasize in a manner specii c to tumor type
and location. For example, breast cancer most ot en metastasizes to the bone.
h ere are many theories on what drives the locations of metastases, such as 'seed
and soil' or mechanical forces (Dittmar
et al
. 2008, Gassmann and Haier 2008,
Brooks
et al.
2009). It is likely that a combination of the two is occurring. Some
in vivo
studies show tumor cells in the circulation occluding capillaries, while
others show tumor cells adhering without blocking blood l ow (Gassmann and
Haier 2008). Chemokine axes are known to be important in homing of tumor
cells to metastatic locations (Kucia
et al.
2005, Dittmar
et al.
2008, Gassmann and
Haier 2008). Many tumor cells, such as breast cancer cells, express CXCR4 and
therefore migrate to areas where the ligand, SDF-1, is expressed, such as bone
(Kucia
et al.
2005). Once at the site, the CXCR4-expressing tumor cells can adhere
through interactions of cell adhesion molecules and transmigrate through the
endothelium into the tissue. As tumor cells circulate, they have to travel through
small capillaries, are forced to change shapes to i t through, and, at times, become
lodged in the capillary. h is puts the surface of the tumor cell in close contact with
