67-kDa laminin receptor in human bile duct carcinoma

Abnormal interaction of epithelial cells with laminin component of basement membrane may account for altered biological behavior of cells, influencing proliferation, adhesion, and motility. In the current study, we investigated the role of 67-kDa laminin receptor (67LR), a high affinity receptor for laminin, in aggressiveness of bile duct carcinoma.

Fifty-two paraffin-embedded specimens and 22 fresh tissues of patients with bile duct carcinoma were analyzed using immunohistologic and real-time polymerase chain reaction techniques, respectively. Expression of 67LR on the bile duct carcinoma QBC939 cells was examined by flow cytometry. The effects of 67LR on the adhesive and invasive abilities of QBC939 cells were determined by adhesion and invasion assay in vitro.

Both at the mRNA and protein level, bile duct carcinoma cells expressed a higher level of 67LR than normal epithelial cells (p < 0.01). The expression of 67LR was correlated inversely with differentiation extent of tumor (p < 0.05). The 67LR level was significantly increased in patients with lymph node metastases than in patients without lymph node involvement (p < 0.01). Flow cytometry showed that 69.9 +/- 1.1% of QBC939 cells expressed 67LR. Expression of 67LR increased the adhesion and invasion of QBC939 cells. 60 and 120 min of incubation of 67LR antibodies, MLuC5, induced 46.3 +/- 2.2 and 61.3 +/- 2.1% inhibition of adhesion, respectively. The invasive ability of QBC939 cells to Matrigel was also reduced by 67LR antibodies, MLuC5.

Overexpressing 67LR on bile duct carcinoma was associated with invasion and metastasis of bile duct carcinoma. Blockage of 67LR suppressed adhesion and invasion of bile duct carcinoma.