BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

Viapiano, Mariano S.; Hockfield, Susan; Matthews, Russell T.

doi:10.1007/s11060-008-9575-8

Cited by 84 publications

(85 citation statements)

References 55 publications

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“…Stable transduction of brevican did not affect cellular proliferation (Fig. 1) or cell morphology (not shown), in agreement with previous results (19,21). However, when we tested the ability of these cells to attach to different substrates representative of the neural ECM and the basal lamina of brain blood vessels, we observed a significant, substrate-dependent effect in brevican-expressing cells.…”

Section: Brevican Promotes Substratedependent Cell Adhesion Andsupporting

confidence: 92%

“…In addition, the following commercial antibodies were used: mouse monoclonal antibodies against fibronectin, N-cadherin, integrin subunits ␤1, ␣V, ␤3, and Tyr 759 -phosphorylated ␤3 (BD Biosciences); mouse monoclonal anti-NCAM and anti-actin (Sigma); rabbit polyclonal anti-epidermal growth factor receptor (EGFR), Tyr , and the C-terminal fragment (signal peptide Met 1 -Ala 22 plus Ser 401 -Pro 911 ) were created by PCR and subcloned in the same vector. The "uncleavable" form of human brevican was created by site-directed mutagenesis to change the sequence 396 ATESESR-GAI 405 to ATESENVYAI, as previously described (21). All constructs were subsequently subcloned into the lentiviral carrier vector pCDH1-MCS-EF1-coGFP (System Biosciences, Mountain View, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Cell Dispersion in Organotypic Cultures-Organotypic cultures of mouse brain slices were essentially performed as described (21). Briefly, postnatal day 1 CD-1 mice (Charles River Laboratories, Wilmington, MA) were decapitated on ice, and their brains were removed into ice-cold HBSS containing 100 units/ml penicillin, 100 g/ml streptomycin, and 250 ng/ml ampothericin.…”

Section: Methodsmentioning

confidence: 99%

“…Motility-The promigratory effects of brevican in gliomas have been described in detail in vivo (19,20,21), but the precise mechanisms underlying these effects remain unclear. Here, we designed experiments to specifically investigate the mechanism(s) by which brevican enhances glioma dispersion.…”

Section: Brevican Promotes Substratedependent Cell Adhesion Andmentioning

confidence: 99%

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The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

Kong

Matthews

et al. 2008

Journal of Biological Chemistry

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The adult neural parenchyma contains a distinctive extracellular matrix that acts as a barrier to cell and neurite motility. Nonneural tumors that metastasize to the central nervous system almost never infiltrate it and instead displace the neural tissue as they grow. In contrast, invasive gliomas disrupt the extracellular matrix and disperse within the neural tissue. A major inhibitory component of the neural matrix is the lectican family of chondroitin sulfate proteoglycans, of which brevican is the most abundant member in the adult brain. Interestingly, brevican is also highly up-regulated in gliomas and promotes glioma dispersion by unknown mechanisms. Here we show that brevican secreted by glioma cells enhances cell adhesion and motility only after proteolytic cleavage. At the molecular level, brevican promotes epidermal growth factor receptor activation, increases the expression of cell adhesion molecules, and promotes the secretion of fibronectin and accumulation of fibronectin microfibrils on the cell surface. Moreover, the N-terminal cleavage product of brevican, but not the full-length protein, associates with fibronectin in cultured cells and in surgical samples of glioma. Taken together, our results provide the first evidence of the cellular and molecular mechanisms that may underlie the motility-promoting role of brevican in primary brain tumors. In addition, these results underscore the important functional implications of brevican processing in glioma progression.Malignant gliomas are primary tumors of the central nervous system with an almost invariably rapid and lethal outcome. Current treatments for gliomas fail to remove the invasive cells that remain diffusely embedded within normal tissue even after aggressive surgical and postsurgical treatment (1). The dispersion of glioma cells is the major cause of disease progression after initial treatment and, therefore, of therapeutic failure.The ability of glioma cells to disperse within the mature central nervous system is unusual, because adult neural tissue is predominantly inhibitory to process extension and cell movement (2, 3). One of the major barriers to cellular movement in the central nervous system is the neural extracellular matrix (ECM).2 This matrix is primarily composed of a scaffold of hyaluronic acid (HA) and associated glycoproteins, with a remarkable absence of fibrillar proteins that support cell motility (2, 4). The inhibitory nature of the neural ECM has been largely attributed to a family of chondroitin sulfate proteoglycans that bind and organize HA within the ECM: aggrecan, neurocan, versican, and brevican, collectively known as lecticans (5-7). It is thought that, to overcome this barrier to movement, glioma cells degrade the normal ECM (8, 9) and secrete mesenchymal matrix components that promote cell adhesion and motility, such as fibronectin and collagens (10 -13). However, surprisingly, gliomas also express large amounts of the inhibitory lecticans versican (14) and brevican (15, 16).Brevican, also known as brain-enrich...

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Section: Brevican Promotes Substratedependent Cell Adhesion Andsupporting

confidence: 92%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Brevican Promotes Substratedependent Cell Adhesion Andmentioning

confidence: 99%

See 2 more Smart Citations

The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

Kong

Matthews

et al. 2008

Journal of Biological Chemistry

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“…This notion is supported by recent studies of glioma cells showing that the G1 domain of brevican generated by ADAMTS cleavage is capable of enhancing cell adhesion and motility. 54,55 Furthermore, TGF␤2-stimulated glioma cell migration was completely blocked by an antibody specific to the ADAMTS-cleaved neo-epitope of V0/V1 versican (amino acid sequence DPEAAE). 56 These findings from glioma progression underscore the important functional implications of proteoglycan processing by ADAMTS proteases in the progression to invasive metastatic cancer.…”

Section: Discussionmentioning

confidence: 99%

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Ricciardelli

Frewin

Tan

et al. 2011

The American Journal of Pathology

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The A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family of proteins is composed of extracellular metalloproteases, including ADAMTS1, originally identified in cachexigenic colon cancer cells. 1,2 Mice with Adamts1-null mutation exhibit urogenital defects and female infertility because of impaired remodeling of ovarian extracellular matrix (ECM), but ovarian steroid production and lactation are normal. 3-5 A range of ECM proteins have been identified as potential ADAMTS1 substrates, including collagens, 6 nidogen, 7 and syndecan-4 8 ; however, the proteoglycans versican and aggrecan have been consistently shown to be key ADAMTS1 targets. 4,9,10 ADAMTS1 processing of versican is important in cell migration during wound healing, 11 endothelial cell invasion, 12 and remodeling of cardiac jelly ECM during heart morphogenesis. 13 These observations indicate that ADAMTS1 mediates acute regulated tissue remodeling processes that occur in development and in adult reproductive tissues, but also in cancer growth and metastasis.Emerging evidence associates ADAMTS1 expression with metastatic potential. Elevated expression of ADAMTS1 is characteristic of breast cancer cell lines 14,15 and human breast cancers with high bone metastatic potential. 16 Likewise, local invasion and lymph node metastasis of pancreatic cancer is associated with elevated Adamts1. 17 Overexpression of full-length ADAMTS1 in

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Overcoming neurite‐inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix

Rowena

Lau

Keough

et al. 2013

Glia

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Acute trauma to the central nervous system (CNS) can result in permanent damage and loss of function related to the poor regeneration of injured axons. Injured axons encounter several barriers to regeneration, such as the glial scar at the injury site. The glial scar contains extracellular matrix (ECM) macromolecules deposited by reactive astrocytes in response to injury. The scar ECM is rich in chondroitin sulfate proteoglycans (CSPGs), macromolecules that inhibit axonal growth. CSPGs consist of a core protein with attachment sites for glycosaminoglycan (GAG) chains. An extensive literature demonstrates that enzymatic removal of the GAG chains by chondroitinase ABC permits some axonal regrowth; however, the remaining intact core proteins also possess inhibitory domains. Because metalloproteinases can degrade core proteins of CSPGs, we have evaluated five matrix metalloproteinases (MMPs) and a related protease-a disintegrin and metalloproteinase with thrombospondin motifs-4 (ADAMTS-4)-for their capacity to overcome CSPG inhibition of neuritic growth in culture. The metalloproteinases were selected for their known expression after CNS injuries. Of the MMPs, MMP-3, -7 and -8 reduced or abolished inhibition of neurite outgrowth on a purified CSPG substrate and on an astrocyte-derived ECM. ADAMTS-4 also attenuated CSPG inhibition of neurites and had the additional benefits of neither degrading laminin nor causing neurotoxicity. The efficacy of ADAMTS-4 matched that of blocking the EGFR signaling previously reported to mediate CSPG inhibition. These findings highlight ADAMTS-4 as a superior protease for overcoming CSPG inhibition of axonal regeneration in the CNS.

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BEHAB/brevican requires ADAMTS-mediated proteolytic cleavage to promote glioma invasion

Cited by 84 publications

References 55 publications

The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

The Proteoglycan Brevican Binds to Fibronectin after Proteolytic Cleavage and Promotes Glioma Cell Motility

The ADAMTS1 Protease Gene Is Required for Mammary Tumor Growth and Metastasis

Overcoming neurite‐inhibitory chondroitin sulfate proteoglycans in the astrocyte matrix

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