ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis

Ohtsuka, Takashi; Shiomi, Takayuki; Shimoda, Masayuki; Kodama, Takahide; Amour, Augustin; Murphy, Gillian; Ohuchi, Eiko; Kobayashi, Koichi; Okada, Yasunori

doi:10.1002/ijc.21324

Cited by 80 publications

(98 citation statements)

References 36 publications

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“…ADAM-28, which cleaves insulin-like growth factor binding protein-3 (IGFBP-3) [112], is found to be about 16-fold over-expressed in NSCLC. This proteinase is mainly present in carcinoma cells and correlates with cancer cell proliferation and lymph node metastasis [113]. ADAM-15, αv and β3 integrins are expressed in small cell lung carcinoma (SCLC) and NSCLC cell lines [114] and ADAM-15 expression is higher in tumoral cells than in normal epithelial cells of pulmonary tumours.…”

Section: Lung Cancermentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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A disintegrin and metalloproteinases (ADAMs) are a recently discovered family of proteins that share the metalloproteinase domain with matrix metalloproteinases (MMPs). Among this family, structural features distinguish the membrane-anchored ADAMs and the secreted ADAMs with thrombospondin motifs referred to as ADAMTSs. By acting on a large panel of membrane-associated and extracellular substrates, they control several cell functions such as adhesion, fusion, migration and proliferation. The current review addresses the contribution of these proteinases in the positive and negative regulation of cancer progression as mainly mediated by the regulation of growth factor activities and integrin functions.

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Section: Lung Cancermentioning

confidence: 99%

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

et al. 2008

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“…On the basis of their close similarity to ADAM8 as well as their redundant roles shown in the other systems, other ADAMs may functionally cooperate with ADAM8. In this regard, the closely related isoform ADAM28s is overexpressed in the human NSCLCs and its high expression levels are correlated with lymph node metastasis (Ohtsuka et al, 2006). More importantly, several ADAMs have been shown to mediate epithelialderived growth factor receptor transactivation induced by G-protein-coupled receptors in various cells or tissues.…”

Section: Discussionmentioning

confidence: 99%

Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer

et al. 2010

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ADAMs (a disintegrin and metalloprotease) are transmembrane proteins involved in a variety of physiological processes and tumorigenesis. Recently, ADAM8 has been associated with poor prognosis of lung cancer. However, its contribution to tumorigenesis in the context of lung cancer metastasis remains unknown. Native ADAM8 expression levels were lower in lung cancer cell lines. In contrast, we identified and characterized two novel spliced isoforms encoding truncated proteins, D18a and D14 0 , which were present in several tumor cell lines and not in normal cells. Overexpression of D18a protein resulted in enhanced invasive activity in vitro. ADAM8 and its D14 0 isoform expression levels were markedly increased in lung cancer cells, in conditions mimicking tumor microenvironment. Moreover, addition of supernatants from D14 0 -overexpressing cells resulted in a significant increase in tartrate-resistant acid phosphatase þ cells in osteoclast cultures in vitro. These findings were associated with increased pro-osteoclastogenic cytokines interleukin (IL)-8 and IL-6 protein levels. Furthermore, lung cancer cells overexpressing D14 0 increased prometastatic activity with a high tumor burden and increased osteolysis in a murine model of bone metastasis. Thus, the expression of truncated forms of ADAM8 by the lung cancer cells may result in the specific upregulation of their invasive and osteoclastogenic activities in the bone microenvironment. These findings suggest a novel mechanism of tumor-induced osteolysis in metastatic bone colonization.

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“…The cDNA was amplified by PCR with primers specific to ADAM-8, ADAM-9, ADAM-10, ADAM-12s, ADAM-12m, ADAM-15, ADAM-17, ADAM-19, ADAM-20, ADAM-21, ADAM-28s, ADAM-28m, ADAM-30, and the housekeeping gene GAPDH, according to our methods (14)(15)(16). Nucleotide sequences of the PCR primers, expected sizes of the amplified cDNA fragments, and positive controls for each ADAM species were previously reported (14)(15)(16).…”

Section: Methodsmentioning

confidence: 99%

“…They are classified into putative proteinase-type and non-proteinase-type ADAMs according to the structural difference of the catalytic site motif in the metalloproteinase domain (5,7). ADAMs may be involved in cell-cell interaction, cell migration, signal transduction, shedding of membrane proteins, and degradation of extracellular matrix under various pathophysiologic conditions such as fertilization (8,9), morphogenesis (10)(11)(12), angiogenesis (13), and cancers (14)(15)(16).…”

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confidence: 99%

“…ADAM-12 is reported to act as a "sheddase" for the precursor form of heparin-binding EGF (18) and to be able to cleave insulin-like growth factor binding protein 3 (IGFBP-3) and IGFBP-5 (19,20). Recent studies have shown that porcine, bovine, and human articular chondrocytes express ADAMs 9,10,12,15,[17][18][19][20][21][22][23][24][25], but there are no reports of systematic analyses of the expression of ADAM members in OA cartilage. In addition, little or no information is available about the mechanism of regulation of ADAM expression or biologic functions in OA cartilage.…”

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confidence: 99%

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ADAM‐12 (meltrin α) is involved in chondrocyte proliferation via cleavage of insulin‐like growth factor binding protein 5 in osteoarthritic cartilage

Okada¹,

Mochizuki²,

Yatabe³

et al. 2008

Arthritis & Rheumatism

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Objective. ADAMs are a gene family of multifunctional proteins. We undertook this study to determine which ADAM species is up-regulated in osteoarthritic (OA) cartilage and to examine its pathobiologic function.Methods. Expression of the 13 different metalloproteinase-type ADAMs was screened by reverse transcription-polymerase chain reaction (PCR), and expression levels of prototype membrane-anchored ADAM-12 (ADAM-12m) were determined by real-time PCR. ADAM-12m expression in articular cartilage was examined by in situ hybridization, immunohistochemistry, and immunoblotting. Chondrocytes were used for functional analyses of ADAM-12m.Results. ADAM-12m was selectively expressed in 87% of OA cartilage, and the expression level was significantly higher in OA cartilage than in normal cartilage. In situ hybridization showed that OA chondrocytes were responsible for the expression. Osteoarthritis (OA) is characterized by the breakdown of articular cartilage, leading to pain and loss of joint function. Articular cartilage is a narrow layer of specialized extracellular matrix, consisting primarily of collagens and proteoglycans, that is elaborated and maintained by a small number of articular chondrocytes. In normal cartilage, chondrocytes sustain a balance between the synthesis and the degradation of matrix components, resulting in stability of the tissue over time. This equilibrium is disturbed in degenerative joint diseases such as OA (1). Chondrocyte cloning, also known as chondrocyte cluster formation, is a major characteristic phenotype of OA cartilage (2), and it could reflect

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ADAM28 is overexpressed in human non-small cell lung carcinomas and correlates with cell proliferation and lymph node metastasis

Cited by 80 publications

References 36 publications

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

Emerging roles of ADAM and ADAMTS metalloproteinases in cancer

Novel alternatively spliced ADAM8 isoforms contribute to the aggressive bone metastatic phenotype of lung cancer

ADAM‐12 (meltrin α) is involved in chondrocyte proliferation via cleavage of insulin‐like growth factor binding protein 5 in osteoarthritic cartilage

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