Molecular interactions of B-CAM (basal-cell adhesion molecule) and laminin in epithelial skin cancer

Abstract

Molecular events underlying the progression of malignant tumors through the surrounding tissue are largely mediated by membrane-bound adhesion molecules. Basal-cell adhesion molecule (B-CAM), a 90-kDa laminin receptor of the immunoglobulin superfamily, is induced in some epithelial malignancies. Its function in these tumors, however, still remains obscure. We demonstrated that expression of B-CAM is very weak, if detectable at all, in normal epidermis but is strongly induced in both basal cell carcinomas and squamous cell carcinomas of the skin, and most pronounced at the basal surface of the tumor nests. Interestingly, the only known B-CAM ligand, laminin, was markedly upregulated within corresponding microanatomical sites surrounding the tumor nests, suggesting that both molecules may interact there. Consistent with this hypothesis, we were able to directly demonstrate binding of a B-CAM/Fc chimeric molecule to the peritumoral stroma in situ. Finally, in proof-of-principle experiments, human B-CAM was overexpressed both in murine and in human fibroblasts. The haptotactic migration of these novel B-CAM+ cell populations on a laminin matrix was significantly increased (P = 0.02) as compared to mock-transfected cells when integrin-mediated adhesion was blocked by chelation of divalent cations. Thus, our findings provide the first direct experimental evidence that interactions of B-CAM and laminin may be involved in progression of epithelial skin tumors.

Protein Kinase A-dependent Phosphorylation of Lutheran/Basal Cell Adhesion Molecule Glycoprotein Regulates Cell Adhesion to Laminin α5

“…The Lu/B-CAM antigens are also expressed in epithelial tissues (11,47). This is consistent with the presence of laminin ␣5 in these tissues (48).…”

“…For example, adhesion mediated by integrin ␣4␤1 results in increased T cell migration via a phosphorylation-mediated interaction with paxillin, a signaling adaptor protein (52). Moreover, it has recently been demonstrated that Lu/B-CAM is functionally involved in skin tumor cell binding and migration through the laminin ␣5 containing stroma (47). Since laminin also appears to increase tumor cell adhesion and migration, it will be of interest to further analyze the impact of Lu phosphorylation on these biological events in normal and pathological epithelial cells.…”

Basal Cell Adhesion Molecule Is Inversely Associated with Apoptosis, but Plays a Limited Role for Protection against Apoptotic Stimuli

“…In complementary experiments, murine 3T3 fibroblasts were chosen as recipients, which show no constitutive expression of B-CAM. As observed recently, human B-CAM was functional in murine cells inasmuch as it conferred laminin-directed adhesion and migration [1,4]. Again, using the pcDNA3.1(-) expression construct, high levels of B-CAM expression were achieved (MFI approximately 300; fig.…”

“…We have previously shown that B-CAM is not expressed in normal epidermis, but is strongly induced de novo in epithelial skin tumors, i.e., basal cell carcinomas and squamous cell carcinomas [3]. In these tumors, B-CAM presumably contributes to local progression through enhanced migration on laminin-containing matrices [4]. However, there are several functional features associated with expression of B-CAM which cannot easily be attributed to the known adhesive function as a laminin receptor.…”

Sex-related Differences in DNA Copy Number Alterations in Hepatitis B Virus-Associated Hepatocellular Carcinoma

“…The chromosomal gain of the 454 Kb window within 19q13.31-q13.32 was also more frequently presented in female HCC cases than in male HCC patients in the present study. Cancer-related genes, such as BCL3, BCAM, and RELB (Drewniok et al, 2004;Maldonado et al, 2010;Slovak et al, 2011) are located in this region.…”