Endothelial Cell Adhesion Molecules and Cancer Progression - Adhesion Molecules - page 336

in cancer progression, it is a dif erent story for sP-selectin. Several studies have
shown that high levels of sP-selectin correlate with tumor progression and indicate
a poor prognosis for patient survival (Table 1) (Kobayashi et al. 2007). What role
is sP-selectin playing in tumor progression? One could argue that sP-selectin
functions as an inhibitor for P-selectin interactions, thereby inhibiting leukocyte
ini ltration and metastasis. However, a recent study demonstrated that sP-selectin
actually increases leukocyte adhesion in an integrin-dependent manner (Woollard
et al. 2008). It will be interesting to determine in future studies whether sP-selectin
enhances tumor cell adhesion, leading to increased metastases. h ese observations
all together point to a complex role for P-selectin, and additional study will lead to
a better understanding of its contribution to cancer progression.

VCAM-1 and ICAM-1 in Cancer Progression

In the rolling process, the weak interactions involving selectins are followed by
stronger interactions of cell adhesion molecules on the endothelium such as
VCAM-1 and ICAM-1 with integrins on the adhering cells. While the role of
these adhesion molecules in ini ltration of leukocytes at sites of inl ammation
is well established, their role in metastasis is still being determined. As with the
selectins, soluble forms of VCAM-1 and ICAM-1 exist. In some types of cancers,
VCAM-1 and ICAM-1 are upregulated, but the soluble forms are upregulated in
many more types of cancers (Table 2) ( Kobayashi et al. 2007). Unlike what has
been suggested with P-selectin, soluble ICAM-1 (sICAM-1) has been indicated
to reduce adhesion, perhaps providing a mechanism to reduce ini ltration of
potentially anti-tumor leukocytes (Kobayashi et al. 2007). Studies have shown that
VCAM-1 mediates tumor cell adhesion and that blocking the molecule can inhibit
this adhesion, indicating a possible role in metastasis (Kobayashi et al. 2007).

Table 2 Levels of VCAM-1 and ICAM-1 detected in cancer patient samples

VCAM-1 sVCAM-1 ICAM-1 sICAM-1

Breast

Colon

Lung

Liver

Gastrointestinal

Kidney

Ovary

Bladder

Lymphoma

Myeloma

Summary from the literature of levels of VCAM-1 and ICAM-1 in samples from cancer patients compared to normal
tissues.

, increased in samples, Ø, decreased in samples.