Cleavage of growth differentiation factor 15 (GDF15) by membrane type 1‐matrix metalloproteinase abrogates GDF15‐mediated suppression of tumor cell growth

El-Aziz, Shaban H. Abd; Endo, Yuichi; Miyamaori, Hisashi; Takino, Takahisa; Sato, Hiroshi

doi:10.1111/j.1349-7006.2007.00547.x

Cited by 22 publications

(19 citation statements)

References 32 publications

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“…Independent of potential ECM substrates, MT1-MMP has been reported to modify cell function by processing integrins, adhesion molecules, cell surface proteoglycans, or surface receptors (Sato et al, 2005;Abd El-Aziz et al, 2007;Basile et al, 2007;Freudenberg and Chen, 2007). In keeping with these observations, we considered the possibility that by exchanging the MT1-MMP catalytic domain with that of the structurally distinct collagenase MMP-1, pericellular collagenolytic activity might be retained, whereas the higher order, functional activity associated with 3-D invasive behavior would be lost.…”

Section: Discussionmentioning

confidence: 99%

Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

Ota

Yana

et al. 2008

MBoC

103

135

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Membrane type-1 matrix metalloproteinase (MT1-MMP) drives cell invasion through three-dimensional (3-D) extracellular matrix (ECM) barriers dominated by type I collagen or fibrin. Based largely on analyses of its impact on cell function under two-dimensional culture conditions, MT1-MMP is categorized as a multifunctional molecule with 1) a structurally distinct, N-terminal catalytic domain; 2) a C-terminal hemopexin domain that regulates substrate recognition as well as conformation; and 3) a type I transmembrane domain whose cytosolic tail controls protease trafficking and signaling cascades. The MT1-MMP domains that subserve cell trafficking through 3-D ECM barriers in vitro or in vivo, however, remain largely undefined. Herein, we demonstrate that collagen-invasive activity is not confined strictly to the catalytic, hemopexin, transmembrane, or cytosolic domain sequences of MT1-MMP. Indeed, even a secreted collagenase supports invasion when tethered to the cell surface in the absence of the MT1-MMP hemopexin, transmembrane, and cytosolic tail domains. By contrast, the ability of MT1-MMP to support fibrin-invasive activity diverges from collagenolytic potential, and alternatively, it requires the specific participation of MT-MMP catalytic and hemopexin domains. Hence, the tissue-invasive properties of MT1-MMP are unexpectedly embedded within distinct, but parsimonious, sequences that serve to tether the requisite matrix-degradative activity to the surface of migrating cells. INTRODUCTIONNormal as well as neoplastic cells traverse interstitial tissues by mobilizing proteolytic enzymes that dissolve intervening structural barriers that are dominated by cross-linked networks of either type I collagen or fibrin (Hiraoka et al., 1998;Chun et al., 2004;Sabeh et al., 2004;Hotary et al., 2006;. Although multiple proteinases have been implicated in tissue-invasive processes, recent studies suggest that the membrane type-1 matrix metalloproteinase (MT1-MMP) plays a critical role in conferring cells with the ability to remodel and penetrate extracellular matrix (ECM) barriers in vivo (Chun et al., 2004;Sabeh et al., 2004;Filippov et al., 2005;Hotary et al., 2006;. Nonetheless, the critical structural and functional properties that imbue MT1-MMP with proinvasive activity and that distinguish it from the bulk of the Ͼ500 proteinases encoded in the mammalian genome remain largely undefined (Puente et al., 2003).Similar in its overall domain structure to the larger family of secreted MMPs, the MT1-MMP zymogen is composed of a propeptide domain, a Zn-containing catalytic domain, a flexible linker peptide, and a hemopexin-like domain near its carboxy terminus . In contrast to the secreted MMPs, however, the MT1-MMP hemopexin domain is extended to include a glutamic acid-rich stem region that connects the extracellular face of the proteinase to a single-pass transmembrane segment that terminates in a short, 20-amino acid cytosolic tail . In its membrane-tethered configuration, studies to date have largely focused on the ability...

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Section: Discussionmentioning

confidence: 99%

Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

Ota

Yana

et al. 2008

MBoC

103

135

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“…15 Therefore, the tissue availability of GDF-15 depends on ECM degradation, histological composition and architecture or presence of enzymes capable of conversion of pro-GDF-15 to GDF-15, implying a regulation similar to TGF-b. 15,16 However, direct binding of GDF-15 to latent TGF-b-binding protein-1, which normally sequesters TGF-b and induces binding to the ECM, has not yet been described. Interestingly, GDF-15 stimulates the expression and surface stabilization of matrix metalloproteinases (MT1-MMP) in different cell types, including breast cancer (MCF-7) or human embryonic kidney cells (HEK293) that are sensitive to GDF-15-induced growth arrest.…”

Section: Gdf-15 Sequence and Structurementioning

confidence: 99%

“…This feedback circuit may have particular significance for ECM remodeling in the tumor environment, tissue permeability in metastatic spreading and for tumor growth. 16 The availability of mature GDF-15 or activation of the proprotein by ECM-deposited and microenvironment-regulated proteinases increases the complexity of the GDF-15 regulatory network in a manner tightly linked to the cell and tissue microenvironment, especially under pathological conditions.…”

Section: Gdf-15 Sequence and Structurementioning

confidence: 99%

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

Vaňhara

Hampl

Kozubı́k

et al. 2012

Prostate Cancer Prostatic Dis

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Deregulation of expression and function of cytokines belonging to the transforming growth factor-b (TGF-b) family is often associated with various pathologies. For example, this cytokine family has been considered a promising target for cancer therapy. However, the detailed functions of several cytokines from the TGF-b family that could have a role in cancer progression and therapy remain unclear. One of these molecules is growth/differentiation factor-15 (GDF-15), a divergent member of the TGF-b family. This stress-induced cytokine has been proposed to possess immunomodulatory functions and its high expression is often associated with cancer progression, including prostate cancer (PCa). However, studies clearly demonstrating the mechanisms for signal transduction and functions in cell interaction, cancer progression and therapy are still lacking. New GDF-15 roles have recently been identified for modulating osteoclast differentiation and for therapy for PCa bone metastases. Moreover, GDF-15 is as an abundant cytokine in seminal plasma with immunosuppressive properties. We discuss studies that focus on the regulation of GDF-15 expression and its role in tissue homeostasis, repair and the immune response with an emphasis on the role in PCa development.

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“…Additionally, Abd El-Aziz et al . (2007) have shown that MT1-MMP contributes to tumor cell proliferation through the cleavage of GDF15, which down-regulates cell proliferation [22]. …”

Section: Discussionmentioning

confidence: 99%

“…Abd El-Aziz et al . demonstrated that MT1-MMP contributes to tumor cell proliferation through the cleavage of growth differentiation factor 15 (GDF15), a transforming growth factor (TGF)-beta superfamily member [22]. Endothelial cells from lungs of one-week-old MMP-14 knockout (MMP14 −/− ) mice show reduced migration and limited ability to form three-dimensional structures on matrigel [17,18,23–25].…”

Section: Introductionmentioning

confidence: 99%

MT1-MMP-Mediated Cleavage of Decorin in Corneal Angiogenesis

et al. 2009

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Background/Aims: Decorin has been shown to have antiangiogenic properties. In this study, we evaluate the involvement of membrane type 1-matrix metalloproteinase (MT1-MMP), a proangiogenic enzyme, in decorin cleavage in the cornea. Methods: MT1-MMP expression was confirmed immunohistochemically in keratocytes and immortalized corneal fibroblast cell lines. Corneal micropockets of bFGF were used to assess the expression of decorin and MT1-MMP. Western blotting was used to evaluate decorin degradation by MT1-MMP. Aortic ring tube formation assays were used to assay the inhibitory effect of decorin and stimulatory effect of MT1-MMP on vascular endothelial cells in vitro. Results: We show that MT1-MMP expression is upregulated following bFGF pellet implantation in the cornea in vivo, and that MT1-MMP cleaves decorin in a time- and concentration-dependent manner in vitro. Furthermore, the addition of MT1-MMP reduces the inhibitory effects of decorin on aortic ring tube formation in vitro. Cleavage of decorin by MT1-MMP-deficient corneal cell lysates is diminished relative to that by wild-type corneal cell lysates, and an MT1-MMP knockin restores decorin processing in vitro. Conclusion: The proangiogenic role of MT1-MMP in the cornea may be mediated, in part, by facilitated cleavage of corneal decorin.

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Cleavage of growth differentiation factor 15 (GDF15) by membrane type 1‐matrix metalloproteinase abrogates GDF15‐mediated suppression of tumor cell growth

Abstract: Growth differentiation factor 15 (GDF15),

Cited by 22 publications

References 32 publications

Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

Molecular Dissection of the Structural Machinery Underlying the Tissue-invasive Activity of Membrane Type-1 Matrix Metalloproteinase

Growth/differentiation factor-15: prostate cancer suppressor or promoter?

MT1-MMP-Mediated Cleavage of Decorin in Corneal Angiogenesis

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