Endothelial Cell Adhesion Molecules and Cancer Progression - Adhesion Molecules - page 329

Tumor progression is intimately linked with host response, being mediated
by interactions of various cell types in the stroma. As such, endothelial cells play
an important role in cancer progression. As with other inl ammatory processes,
ini ltrating cells must i rst cross endothelial cells to get to the tumor. Leukocytes
are recruited to the primary tumor site and extravasate to the tissue using a rolling
mechanism (Fig. 2) . h e circulating leukocytes i rst interact loosely with selectins
and start rolling along the endothelium. As the cells roll, i rm interaction occurs
through cell adhesion molecules, and subsequently, transendothelial migration
ensues. Similarly, tumor cells must intravasate from the primary site and then
cross endothelial cells at distant sites to create metastases, or secondary tumor
growths. h ough the extravasation of tumor cells is not as well characterized as
that of leukocytes, the mechanisms seem to have some characteristics in common
(Fig. 3A) . Some studies indicate that tumor cells do not roll like leukocytes,
but tumor cells express adhesion molecules similar to leukocytes, leading to
the hypothesis that these cells interact directly with the endothelium (Fig. 3B)
(Gassmann and Haier 2008). However, there are some studies indicating that
tumor cells are clustered with leukocytes in circulation, and that the leukocytes
mediate extravasation through their own cell adhesion molecules (Gassmann
and Haier 2008) (Fig. 3C) . Other studies suggest that tumor cell interactions with
platelets mediate adhesion (Gassmann and Haier 2008).

Fig. 2 Leukocyte adhesion to endothelium. Leukocytes adhere to endothelium through
a mechanism described as rolling adhesion. As the leukocyte moves with blood l ow, mucin
molecules on its surface interact with E- or P-selectin on the endothelium, allowing loose
adhesion. h is interaction leads to cell rolling along the endothelium, exposing integrins on the
leukocyte to cell adhesion molecules, such as ICAM and VCAM, on the endothelium, mediating
strong adhesion. h

e leukocyte is then able to undergo transendothelial migration and move into

the tissue.