Effect of ADAM28 on Carcinoma Cell Metastasis by Cleavage of von Willebrand Factor

Mochizuki, Satsuki; Soejima, Kenji; Shimoda, Masayuki; Abe, Hitoshi; Sasaki, Aya; Okano, Hirotaka James; Okano, Hideyuki; Okada, Yasunori

doi:10.1093/jnci/djs232

Cited by 90 publications

(108 citation statements)

References 49 publications

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“…A related enzyme, the ADAM-28 from carcinoma cells, can hydrolyze VWF at different peptide bonds as well [52]. Our data showing that also ADAM-10 and ADAM-17 can cleave VWF at least at two peptide bonds, deserve further characterization on cleavage sites.…”

mentioning

confidence: 60%

Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count

Lancellotti

Dragani

Ranalli

et al. 2015

Journal of Thrombosis and Haemostasis

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mentioning

confidence: 60%

Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count

Lancellotti

Dragani

Ranalli

et al. 2015

Journal of Thrombosis and Haemostasis

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“…92 To-date, only a limited number of substrates has been identified for ADAM28 protease activity. These include von Willebrand factor (VWF), 93 CD23 94 and insulin-like growth factor binding protein-3. 95 In addition to its proteolytic activity, ADAM28 interacts with several integrins including alpha4beta1, alpha4beta7 and alpha9beta1, suggesting that in addition to proteolysis, it may also play a role in cell adhesion.…”

Section: Adam28mentioning

confidence: 99%

The ADAMs family of proteases as targets for the treatment of cancer

Mullooly

McGowan

Crown

et al. 2016

Cancer Biology & Therapy

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The ADAMs (a disintegrin and metalloproteases) are transmembrane multidomain proteins implicated in multiple biological processes including proteolysis, cell adhesion, cell fusion, cell proliferation and cell migration. Of these varied activities, the best studied is their role in proteolysis. However, of the 22 ADAMs believed to be functional in humans, only approximately a half possess matrix metalloproteinase (MMP)-like protease activity. In contrast to MMPs which are mostly implicated in the degradation of extracellular matrix proteins, the main ADAM substrates are the ectodomains of type I and type II transmembrane proteins. These include growth factor/cytokine precursors, growth factor/cytokine receptors and adhesion proteins. Recently, several different ADAMs, especially ADAM17, have been shown to play a role in the development and progression of multiple cancer types. Consistent with this role in cancer, targeting ADAM17 with either low molecular weight inhibitors or monoclonal antibodies was shown to have anticancer activity in multiple preclinical systems. Although early phase clinical trials have shown no serious side effects with a dual ADAM10/17 low molecular weight inhibitor, the consequences of long-term treatment with these agents is unknown. Furthermore, efficacy in clinical trials remains to be shown.

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“…Another substrate of ADAM28 was connective tissue growth factor (CTGF), and its digestion by ADAM28 led to release of vascular endothelial growth factor165 (VEGF165) from the CTGF/VEGF165 complex, causing activation of angiogenesis 13) . ADAM28 also degraded von Willebrand factor (VWF), which induced apoptosis in human carcinoma cell lines with negligible ADAM28 expression, and this digestion by ADAM28-expressing carcinoma cells enabled them to escape from VWF-induced apoptosis 14) . Downregulation of ADAM28 by siRNA, shRNA or mouse anti-ADAM28 antibody suppressed growth and lung metastasis of intravenously injected lung adenocarcinoma cells in nonobese diabetic/severe combined immunodeficiency (NOD/SCID) mice.…”

Section: Substrates and Functions Of Adam28 In Carcinoma Cell Prolifementioning

confidence: 99%

Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment

Okada

2017

Juntendo Medical Journal

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A disintegrin and metalloproteinase 28 (ADAM28) is overexpressed predominantly by carcinoma cells in more than 70% of the non-small cell lung carcinomas, showing positive correlations with carcinoma cell proliferation and metastasis. ADAM28 cleaves insulin-like growth factor binding protein-3 (IGFBP-3) in the IGF-I/IGFBP-3 complex, leading to stimulation of cell proliferation by intact IGF-I released from the complex. ADAM28 also degrades von Willebrand factor (VWF), which induces apoptosis in human carcinoma cell lines with negligible ADAM28 expression, and the VWF digestion by ADAM28-expressing carcinoma cells facilitates them to escape from VWF-induced apoptosis, resulting in promotion of metastasis. We have developed human antibodies against ADAM28 and shown that one of them significantly inhibits tumor growth and metastasis using lung adenocarcinoma cells. Our data suggest that ADAM28 may be a new molecular target for therapy of the patients with ADAM28-expressing non-small cell lung carcinoma.

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Effect of ADAM28 on Carcinoma Cell Metastasis by Cleavage of von Willebrand Factor

Abstract: ADAM28 cleaves and inactivates proapoptotic VWF in carcinoma cells and enhances lung metastasis probably by promoting carcinoma cell survival within the blood vessels.

Cited by 90 publications

References 49 publications

Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count

Qualitative and quantitative modifications of von Willebrand factor in patients with essential thrombocythemia and controlled platelet count

The ADAMs family of proteases as targets for the treatment of cancer

Peking University - Juntendo University Joint Symposium on Cancer Research and Treatment

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