ADAM8 as a novel serological and histochemical marker for lung cancer

Kanagawa Cancer Center, Yokohama, Kanagawa, Japan
Clinical Cancer Research (Impact Factor: 8.72). 01/2005; 10(24):8363-70. DOI: 10.1158/1078-0432.CCR-04-1436
Source: PubMed


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

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Available from: Nobuhisa Ishikawa
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    • "Increased expression of ADAMs and ADAMTS has been detected in numerous tumors. ADAM-8, -12, -15 and -28 are highly expressed in non-small cell lung cancer [7], [8], [9], [10], ADAM-9, -12, -17 and -23 are highly expressed in breast cancer [11], [12], [13], [14] and ADAM-9, -12 and -17 are highly expressed in liver cancer [15], [16], [17]. ADAMTS4 and ADAMTS5 have been reported to be involved in the metastatic process by cleaving brevican in glioblastomas [18]. "
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    • "Ishikawa et al. showed that in squamous cell carcinomas of the lung ADAM8 was significantly overexpressed compared to a healthy control group [11]. They also showed that transfection of ADAM8 into tumor cells elevated the invasiveness [2]. "
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    • "A total of nine frozen primary lung cancer tissues for RNA extraction were obtained as published earlier [18,19]. Formalin-fixed primary lung tumors and adjacent normal lung tissue samples used for immunostaining on tissue microarrays had been obtained from 331 patients undergoing curative surgery at Saitama Cancer Center (Saitama, Japan) [20,21]. To be eligible for this study, tumor samples were selected from patients who fulfilled all of the following criteria: (a) patients suffered primary NSCLC with histologically confirmed stage (only pT1 to pT4, pN0 to pN2, and pM0); (b) patients underwent curative surgery, but did not receive any preoperative treatment; (c) among them, NSCLC patients with positive lymph node metastasis (pN1-pN3) were treated with platinum-based adjuvant chemotherapies after surgical resection, whereas patients with pN0 did not receive adjuvant chemotherapies; and (d) patients whose clinical follow-up data were available. "
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