Immunoglobulin Superfamily Of Cell Adhesion Molecules

Members of the immunoglobulin superfamily of cell adhesion molecules (Ig-CAM) have 1-7 extracellular immunoglobulin-like domains. They are attached to the plasma membrane by a single, hydrophobic transmembrane sequence and have a cytoplasmic tail (7). They can be involved in both homotypic and heterotypic adhesion (84).

3.1 ALCAM

ALCAM (activated leukocyte cell adhesion molecule, CD166, human melanoma metastasis clone D [MEMD], HB2) is a glycoprotein of the immunoglobulin superfamily that is involved in both homotypic/homo-philic adhesion and heterotypic/heterophilic (to CD6) adhesion (85, 86). In a study of 120 primary breast carcinomas, levels, of ALCAM RNA transcripts (by real-time PCR) were analyzed in relation to clinical data from a 6-year follow-up period (87). Decreased levels of ALCAM correlated with nodal involvement, higher grade, higher TNM (tumor, node, metastasis) stage, worse NPI (Nottingham Prognostic Index), and clinical outcome (local recurrence and death due to breast cancer). Burkhardt et al. (88) performed an immunohistochemical study of 162 primary breast carcinomas and correlated the staining pattern with the clinical findings (Figure 1). There was a mean follow-up period of 53 months. Both intraductal and invasive breast carcinomas had higher ALCAM expression than normal breast. High cytoplasmic ALCAM expression was associated with shortened patient disease-free survival.

Jezierska et al. (89) used laser scanning cytometry and confocal microscopy to evaluate 56 breast cancer specimens. The results were correlated to clinical and pathologic data from the cases. High levels of ALCAM correlated with small tumor diameter, low tumor grade, presence of progesterone receptor, and presence of estrogen receptors. Lower levels of ALCAM were associated with HER2/neu gene amplification (but the numbers were not statistically significant). Small tumors and those with low tumor grade had higher ALCAM/MMP-2 ratios. In a separate report the same research group (90) found that ALCAM-ALCAM interactions between breast cancer cells is important for survival in the primary tumor. Loss of ALCAM is associated with programmed cell death, both apoptosis and autophagy.

3.2 VCAM-1

VCAM-1 (vascular cell adhesion molecule-1) is involved in heterotypic adhesion. VCAM-1 is increased in the tumor cytosol and sera of

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