ADAM8 as a novel serological and histochemical marker for lung cancer.
OBJECTIVE
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.
Ishikawa
Nobuhisa
N
Laboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, The University of Tokyo, Tokyo, Japan.
Daigo
Yataro
Y
Yasui
Wataru
W
Inai
Kouki
K
Nishimura
Hitoshi
H
Tsuchiya
Eiju
E
Kohno
Nobuoki
N
Nakamura
Yusuke
Y
D051722:ADAM Proteins; D000230:Adenocarcinoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D019556:COS Cells; D002272:Carcinoembryonic Antigen / Q000378:metabolism; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016022:Case-Control Studies; D002465:Cell Movement; D002522:Chlorocebus aethiops; D003094:Collagen / Q000378:metabolism; D004338:Drug Combinations; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007797:Laminin / Q000378:metabolism; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008875:Middle Aged; D041681:NIH 3T3 Cells; D009361:Neoplasm Invasiveness; D011379:Prognosis; D011509:Proteoglycans / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012699:Serology; D014162:Transfection
D015703:Antigens, CD; D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D004338:Drug Combinations; D007797:Laminin; D008565:Membrane Proteins; D011509:Proteoglycans; D012333:RNA, Messenger; C059485:matrigel; D003094:Collagen; D051722:ADAM Proteins; C068490:ADAM8 protein, human; D008666:Metalloendopeptidases