ABSTRACT
Endothelial cell adhesion molecules play an integral role in adhesion and infi ltration of leukocytes into tissues, which is important to immune function. Th ey also play an important role in cancer progression. Cancer progression involves many processes, beginning with proliferation of the tumor cells at the primary site. Leukocytes are recruited into the primary tumors by tumor-secreted factors, mediating pro-and anti-tumor responses, as well as secreting factors themselves that lead to more recruitment. Leukocytes are also known to promote vascularization of the tumor, another key step in cancer progression. Later in cancer progression, the tumor cells intravasate and circulate, eventually adhering to the endothelium at distant organ sites, where they can extravasate and form
metastases. Tumor cells are known to express adhesion molecules similar to those found on leukocytes, expressing molecules containing sialyl Lewis determinants, implicating the reciprocal endothelial cell adhesion molecules, E-selectin and P-selectin, in this process. Indeed, E-selectin and P-selectin levels are increased in cancer patients. Th e endothelial cell adhesion molecules intercellular adhesion molecule 1 (ICAM-1) and vascular cell adhesion molecule 1 (VCAM-1) are found to be upregulated in cancer patients, and tumor cells express many integrins, the ligands for these adhesion molecules. Clinical and research data indicate that endothelial cell adhesion molecules are major players in metastasis. Th is chapter will outline the roles that endothelial cell adhesion molecules play in cancer progression.
