ADAM15, a member of the ADAM (a
disintegrin and
metalloprotease) family, is a
membrane protein containing both
protease and adhesion domains and may, thus, be involved in
tumor invasion and
metastasis. The aim of this study was to analyze the expression of ADAM15 and its potential
ligand,
integrin alpha(v)beta3 (CD51/CD61), in lung
carcinoma cell lines and tissues. Most small cell lung
carcinomas (SCLCs) and non-SCLC cell lines were ADAM15, alpha(v) and
beta3 integrin mRNA positive. Half of the cell lines expressed ADAM15, and three expressed the alpha(v)beta3 heterodimer at the cell surface as shown using flow cytometry.
Paraffin sections of pulmonary epithelial
tumors, including SCLCs (n=26),
squamous cell cancer (SCCs, n=27) and
adenocarcinomas (ACs, n=17) were stained with
antibodies to the ectosolic and cytosolic domain of ADAM15 and alpha(v)
beta3 integrin complex. The results were scored (0-12, according to Remmele's score). Normal epithelial cells of the lung were negative or slightly positive for ADAM15 (score<2). The score was always significantly higher for
tumor cells. ACs showed the strongest staining (
tumor center; ADAM15ecto; mean+/-SEM; 5.47+/-1.04), whereas SCLCs only showed weak ADAM15 expression (2.67+/-0.42; SCCs: 3.62+/-0.62). Frequently, significantly stronger ADAM15 expression has been shown in
tumor cells located at the front of invasion compared with those within solid formations. Overall analysis of all
tumor specimens and each
tumor type revealed no significant correlation between
tumor stage or degree of differentiation and ADAM15 ectosolic or cytosolic domain expression in
tumor cells. Both molecules are often co-localized in the same
tumor cells in ADAM15- and alpha(v)
beta3 integrin-positive
carcinomas. In summary, lung
carcinoma cell lines and tissues were frequently ADAM15 positive.