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ADAM8 as a Novel Serological and Histochemical Marker for Lung Cancer

¹ Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo; Departments of ² Molecular and Internal Medicine, ³ Molecular Pathology, and ⁴ Pathology, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima; ⁵ Department of Thoracic Surgery, Saitama Cancer Center, Saitama; and ⁶ Kanagawa Cancer Center Research Institute, Kanagawa, Japan

Purpose and Experimental Design: We have been investigating genes involved in pulmonary carcinogenesis by examining gene expression profiles of non–small-cell lung cancers to identify molecules that might serve as diagnostic markers or targets for development of new molecular therapies. A gene encoding ADAM8, a disintegrin and metalloproteinase domain-8, was selected as a candidate for such molecule. Tumor tissue microarray was applied to examine expression of ADAM8 protein in archival lung cancer samples from 363 patients. Serum ADAM8 levels of 105 lung cancer patients and 72 controls were also measured by ELISA. A role of ADAM8 in cellular motility was examined by Matrigel assays.

Results: ADAM8 was abundantly expressed in the great majority of lung cancers examined. A high level of ADAM8 expression was significantly more common in advanced-stage IIIB/IV adenocarcinomas than in adenocarcinomas at stages I–IIIA. Serum levels of ADAM8 were significantly higher in lung cancer patients than in healthy controls. The proportion of the serum ADAM8-positive cases defined by our criteria was 63% and that for carcinoembryonic antigen was 57%, indicating equivalent diagnostic power of these two markers. A combined assay using both ADAM8 and carcinoembryonic antigen increased sensitivity because 80% of the lung cancer patients were then diagnosed as positive, whereas only 11% of 72 healthy volunteers were falsely diagnosed as positive. In addition, exogenous expression of ADAM8 increased the migratory activity of mammalian cells, an indication that ADAM8 may play a significant role in progression of lung cancer.

Conclusions: Our data suggest that ADAM8 should be useful as a diagnostic marker and probably as a therapeutic target.

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