The Metallo-Disintegrin ADAM10 (MADM) from Bovine Kidney Has Type IV Collagenase Activityin Vitro

Millichip, Mark; Dallas, D. J.; Wu, Erxi; Dale, Stephanie; McKie, Norman

doi:10.1006/bbrc.1998.8485

Cited by 113 publications

(85 citation statements)

References 26 publications

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“…A previous study has demonstrated that ADAM10 promotes the proliferation of gastric cancer cells by mediating ectodomain shedding and, therefore, activating epidermal growth factor receptor ligands (25). Other studies have demonstrated that ADAM10 plays a role in the hydrolysis of placental type IV collagen, an important extracellular matrix component, further indicating that ADAM10 is involved in cancer invasion and metastasis (33).…”

Section: Discussionmentioning

confidence: 99%

Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

Qiu

Xiong

et al. 2015

Oncology Letters

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Abstract. The aim of the present study was to determine the expression of a-disintegrin and metalloproteinase 10 (ADAM10) in human glioma tissues from surgical specimens and discuss its possible significance in glioma biology. A total of 43 glioma specimens obtained from patients between 2007 and 2010 were collected and a series of assays were performed. Of these, 22 cases were low-grade gliomas, while 21 cases were high-grade gliomas. In addition, 20 cases of meningioma were used as the control group. Reverse transcription-polymerase chain reaction (RT-PCR), western blot analysis and immunohistochemistry were used to determine the mRNA and protein expression levels of ADAM10. Besides the quantitative analysis, histological observations were also performed to localize ADAM10 expression in glioma cells. The RT-PCR and western blot analysis results demonstrated increased ADAM10 expression in the low-grade glioma samples compared with the control (P<0.05), while ADAM10 expression was further increased in the high-grade glioma samples (P<0.01 vs. control; P<0.05 vs. low-grade glioma), indicating that the mRNA and protein expression levels of ADAM10 were malignancy-dependent. The immunohistochemical analysis revealed that the ADAM10 protein was located on both the tumor cell membrane and blood vessel walls within tumor tissues. In conclusion, these results indicated that ADAM10 expression correlates with the grade of malignancy in human glioma from surgical specimens. In addition, the fact that ADAM10 protein was expressed on cell membranes and blood vessel walls within tumor tissues, indicates that its expression may be associated with invasive tumor growth and peritumoral edema formation.

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Section: Discussionmentioning

confidence: 99%

Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

Qiu

Xiong

et al. 2015

Oncology Letters

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“…This is an interesting finding given that proteases that degrade ECM components have been implicated in tumor growth and invasion as a function of their ability to degrade the basement membrane. Several other members of the ADAM family including ADAM 10, ADAM 15, and the closely related snake venom metalloprotease have been reported to have type IV collagen-and gelatin-degrading properties (21)(22)(23). Recently ADAM 13 has been reported to cleave fibronectin (24).…”

Section: Discussionmentioning

confidence: 99%

ADAM 12 Cleaves Extracellular Matrix Proteins and Correlates with Cancer Status and Stage

Roy

Wewer

Zurakowski

et al. 2004

Journal of Biological Chemistry

221

214

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ADAM 12 is a member of a family of disintegrincontaining metalloproteases that have been implicated in a variety of diseases including Alzheimer's disease, arthritis, and cancer. We purified ADAM 12 from the urine of breast cancer patients via Q-Sepharose anion exchange and gelatin-Sepharose affinity chromatography followed by protein identification by matrix-assisted laser desorption/ionization-time of flight mass spectrometry. Four peptides were identified that spanned the amino acid sequence of ADAM 12. Immunoblot analysis using ADAM 12-specific antibodies detected an ϳ68-kDa band identified as the mature form of ADAM 12. To characterize catalytic properties of ADAM 12, full-length ADAM 12-S was expressed in COS-7 cells and purified. Substrate specificity studies demonstrated that ADAM 12-S degrades gelatin, type IV collagen, and fibronectin but not type I collagen or casein. Gelatinase activity of ADAM 12 was completely abrogated by zinc chelators 1,10-phenanthroline and EDTA and was partially inhibited by the hydroxamate inhibitor Marimastat. Endogenous matrix metalloprotease inhibitor TIMP-3 inhibited activity. To validate our initial identification of this enzyme in human urine, 117 urine samples from breast cancer patients and controls were analyzed by immunoblot. The majority of samples from cancer patients were positive for ADAM 12 (67 of 71, sensitivity 0.94) compared with urine from controls in which ADAM 12 was detected with significantly lower frequency. Densitometric analyses of immunoblots demonstrated that ADAM 12 protein levels were higher in urine from breast cancer patients than in control urine. In addition, median levels of ADAM 12 in urine significantly increased with disease progression. These data demonstrate for the first time that ADAM 12 is a gelatinase, that it can be detected in breast cancer patient urine, and that increased urinary levels of this protein correlate with breast cancer progression. They further support the possibility that detection of urinary ADAM 12 may prove useful in the development of noninvasive diagnostic and prognostic tests for breast and perhaps other cancers. ADAMs1 (a disintegrin and metalloprotease) are a family of integral membrane and secreted glycoproteins that are related to snake venom metalloproteases and matrix metalloproteases (MMPs). These proteases are multidomain proteins composed of a prodomain, metalloprotease domain, disintegrin domain, and a cysteine-rich region, and membrane-anchored ADAMs also contain a transmembrane and cytoplasmic domain. ADAMs display diverse roles in cell surface remodeling, ectodomain shedding, regulation of growth factor availability, and in mediating cell-cell and cell-matrix interactions in both normal development and pathological states such as Alzheimer's disease, arthritis, cancer, and cardiac hypertrophy (1-3). Human ADAM 12 is expressed as two alternatively spliced forms: a membrane-anchored long form (ADAM 12-L) and a shorter secreted form (ADAM 12-S) (4). ADAM 12-S is an active protease known to cleave IGF...

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“…The metalloprotease domain of ADAMs has been shown to induce ectodomain shedding (a specialized type of limited proteolysis) of various membrane-bound proteins (e.g., cytokines and growth factors, cytokine and growth factor receptors, and adhesion molecules) in vitro and in vivo, whereas the disintegrin and cysteine-rich domains have adhesive properties in that they interact with integrins on the opposing cell surface (Seals and Courtneidge, 2003;White, 2003). Selected ADAM proteins have also been reported to degrade ECM proteins (Millichip et al, 1998;Alfandari et al, 2001;Martin et al, 2002;White, 2003) to facilitate cell migration. On the other hand, the cytoplasmic tails are divergent and contain several potential phosphorylation sites, as well as binding sites for Src homology region 3 domain-containing proteins (Seals and Courtneidge, 2003), which may ultimately regulate the ability of an ADAM to cleave a specific substrate.…”

Section: Cytokines and Growth Factorsmentioning

confidence: 99%

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

2008

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The Metallo-Disintegrin ADAM10 (MADM) from Bovine Kidney Has Type IV Collagenase Activityin Vitro

Cited by 113 publications

References 26 publications

Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

Expression of a-disintegrin and metalloproteinase 10 correlates with grade of malignancy in human glioma

ADAM 12 Cleaves Extracellular Matrix Proteins and Correlates with Cancer Status and Stage

Anchoring Junctions As Drug Targets: Role in Contraceptive Development

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