ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function

Shindo, Takayuki; Kurihara, Hiroki; Kuno, Kouji; Yokoyama, Hitoshi; Wada, Takashi; Kurihara, Yukiko; Imai, Tetsuo; Wang, Yuhui; Ogata, Masafumi; Nishimatsu, Hiroaki; Moriyama, Nobuo; Oh-hashi, Yoshio; Morita, Hiroyuki; Ishikawa, Takatoshi; Nagai, Ryozo; Yazaki, Yoshio; Matsushima, Kouji

doi:10.1172/jci8635

Cited by 288 publications

(205 citation statements)

References 28 publications

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“…Inhibition of VEGF signaling may therefore represent one possible mechanism of the antiangiogenic effect of ADAMTS-1 in vivo. 126 However, studies using Adamts1-null mice show essential roles for ADAMTS-1 in organogenesis, 127 yet these mice do not show a phenotype consistent with the antiangiogenic activities of ADAMTS-1 described above. 127 Either the antiangiogenic function of ADAMTS-1 is not important physiologically, or there are mechanisms that compensate for its loss.…”

Section: The Modus Operandi Proangiogenic Activities Of Metalloproteimentioning

confidence: 96%

Metalloproteinases and their inhibitors in tumor angiogenesis

Handsley

Edwards

2005

Intl Journal of Cancer

259

211

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Angiogenesis is the process by which new blood vessels are formed from preexisting vasculature. It is an essential feature of the female reproductive cycle, embryonic development and wound repair. Angiogenesis has also been identified as a causal or contributing factor in several pathologies, including cancer, where it is a rate-limiting step during tumor progression. Matrix metalloproteinases (MMPs) are a family of soluble and membrane-anchored proteolytic enzymes that can degrade components of the extracellular matrix (ECM) as well as a growing number of modulators of cell function. Several of the MMPs, in particular the gelatinases and membrane-type 1 MMP (MT1-MMP), have been linked to angiogenesis. Potential roles for these proteases during the angiogenic process include degradation of the basement membrane and perivascular ECM components, unmasking of cryptic biologically relevant sites in ECM components, modulation of angiogenic factors and production of endogenous angiogenic inhibitors. This review brings together what is currently known about the functions of the MMPs and the closely related ADAM (a disintegrin and metalloproteinase domain) and ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) families in angiogenesis and considers how this information might be useful in manipulation of the angiogenic process, with a view to constraining tumor progression. ' 2005 Wiley-Liss, Inc.Key words: metalloproteinase; tumor; angiogenesis; tissue inhibitor of metalloproteinases; protease; extracellular matrix Angiogenesis is an essential feature of several physiologic processes such as the developmental growth of organs, wound healing and the female reproductive cycle. 1 It is also particularly significant in cancer progression, being a crucial step in the transition of a tumor from a hyperplastic but contained in situ state to a malignant phenotype. 2,3 To allow its growth beyond a certain critical size, a solid avascular tumor must develop its own blood supply in order to meet its growing metabolic requirements. 1 Vascularization of a tumor also provides a route for dissemination of the tumor cells to different sites around the body.Although angiogenesis appears to be the primary form of tumor vascularization, the malignant cells of a tumor can gain access to a blood supply through other means, such as via tumor-induced vasculogenesis, in which bone marrow-derived precursor endothelial cells contribute to the formation of tumor vessels. 4,5 Vasculogenic mimicry is another form of vessel formation that has been reported in certain tumor types, such as aggressive human uveal melanomas, prostate and breast tumors. [6][7][8] In these cases, networks of tumor cell-lined vascular channels were identified within the tumors. Finally, vessel co-option, implemented by tumor cells as a temporary means of gaining access to a blood supply, involves the tumor cells growing around and thus co-opting existing host vessels to form an initially well-vascularized tumor. 9 This review will highlight new insigh...

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Section: The Modus Operandi Proangiogenic Activities Of Metalloproteimentioning

confidence: 96%

Metalloproteinases and their inhibitors in tumor angiogenesis

Handsley

Edwards

2005

Intl Journal of Cancer

259

211

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“…There are at least 19 members of the ADAMTS family, of which ADAMTS-1 was the first to be identified. Disruption of the Adamts-1 gene in mice results in reduced growth, abnormalities in ureteral, adrenal and adipose tissues, and infertility in female mice (Shindo et al, 2000).…”

Section: Introductionmentioning

confidence: 99%

Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively

2005

Oncogene

147

156

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The exact role of a disintegrin and metalloproteinase with thrombospondin motifs-1 (ADAMTS-1) and the underlying mechanism of its involvement in tumor metastasis have not been established. We have now demonstrated that overexpression of ADAMTS-1 promotes pulmonary metastasis of TA3 mammary carcinoma and Lewis lung carcinoma cells and that a proteinase-dead mutant of ADAMTS-1 (ADAMTS-1E/Q) inhibits their metastasis, indicating that the prometastatic activity of ADAMTS-1 requires its metalloproteinase activity. Overexpression of ADAMTS-1 in these cells promoted tumor angiogenesis and invasion, shedding of the transmembrane precursors of heparin-binding epidermal growth factor (EGF) and amphiregulin (AR), and activation of the EGF receptor and ErbB-2, while overexpression of ADAMTS-1E/Q inhibited these events. Furthermore, we found that ADAMTS-1 undergoes auto-proteolytic cleavage to generate the NH 2 -and COOH-terminal cleavage fragments containing at least one thrombospondin-type-I-like motif and that overexpression of the NH 2 -terminal ADAMTS-1 fragment and the COOH-terminal ADAMTS-1 fragment can inhibit pulmonary tumor metastasis. These fragments also inhibited Erk1/2 kinase activation induced by soluble heparin-binding EGF and AR. Taken together, our results suggest that the proteolytic status of ADAMTS-1 determines its effect on tumor metastasis, and that the ADAMTS-1E/Q and the ADAMTS-1 fragments likely inhibit tumor metastasis by negatively regulating the availability and activity of soluble heparin-binding EGF and AR.

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“…We have shown that this homology can contribute to interactions between papilin and an ADAMTS metalloprotease (Kramerova et al, 2000, and unpublished observations in this laboratory). ADAMTS metalloproteases have been conserved during evolution, and in C. elegans and mouse some are essential for correct organogenesis (Blelloch and Kimble, 1999;Shindo et al, 2000;Kuno et al, 2002). Other mammalian ADAMTS proteases participate in remodeling and degradation of vertebrate ECM (Tortorella et al, 1999;Levy et al, 2001), and influence angiogenesis (Vazquez et al, 1999).…”

Section: Introductionmentioning

confidence: 99%

Alternative splicing of papilin and the diversity of Drosophila extracellular matrix during embryonic morphogenesis

Kramerova

Kramerov

Fessler

2003

Developmental Dynamics

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Papilins are extracellular matrix proteins that share a particular, common order of types of protein domains. They occur widely, from nematodes to man, and can differ in the number of repeats of a given type of domain. Protein variety is increased by differential splicing of pre-mRNA. We report that Drosophila, which has a compact genome, expresses three splice variants of papilin during embryogenesis in developmentally defined patterns. These isoforms have different numbers of Kunitz and IgC2 domains. The papilin isoforms are expressed in specific cell types and contribute to different extracellular matrices in gastrulation folds, early mesoderm, heart formation, basement membranes, and elaboration of the excorporeal peritrophic membrane that lines the gut. This finding indicates an unexpectedly broad spectrum of different pericellular matrices in Drosophila embryos. Such papilin-containing matrices have developmental as well as functional significance, as we previously showed that both suppression of papilin synthesis and ectopic overexpression lethally disrupt organogenesis. Developmental Dynamics 226:634 -642, 2003.

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ADAMTS-1: a metalloproteinase-disintegrin essential for normal growth, fertility, and organ morphology and function

Cited by 288 publications

References 28 publications

Metalloproteinases and their inhibitors in tumor angiogenesis

Metalloproteinases and their inhibitors in tumor angiogenesis

Full-length ADAMTS-1 and the ADAMTS-1 fragments display pro- and antimetastatic activity, respectively

Alternative splicing of papilin and the diversity of Drosophila extracellular matrix during embryonic morphogenesis

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