Selective Hydrolysis of Triple-helical Substrates by Matrix Metalloproteinase-2 and -9

Lauer‐Fields, Janelle L.; Sritharan, Thilaka; Stack, M. Sharon; Nagase, Hideaki; Fields, Gregg B.

doi:10.1074/jbc.m211330200

Cited by 92 publications

(127 citation statements)

References 52 publications

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“…6A), with greater activity found in response to CD44. This activity was completely inhibited by EDTA (data not shown), suggesting metalloproteinase activity (41). The MMP-14 selective substrate C 10 -(Gly-ProHyp) 5 -Gly-Pro-Lys(Mca)-Gly-Pro-Gln-GlyϳCys(4-methoxybenzyl)-Arg-Gly-Gln-Lys(Dnp)-Gly-Val-Arg-(Gly-Pro-Hyp) 5 -NH 2 was used for comparison with general triple-helical peptidase activity.…”

Section: Resultsmentioning

confidence: 83%

“…The reagents for RT-PCR were all purchased through Invitrogen, and all of the immunologicals were supplied by Chemicon International (Temecula, CA). MMPs used as standards were expressed, purified, or purchased as described (41). 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate, 1-hydroxybenzotriazole, and 9-fluorenylmethoxycarbonyl-amino acid derivatives were obtained from Novabiochem (San Diego, CA).…”

Section: Methodsmentioning

confidence: 99%

“…Hexanoic acid (CH 3 -(CH 2 ) 4 -CO 2 H, designated C 6 ) and decanoic acid (CH 3 -(CH 2 ) 8 -CO 2 H, designated C 10 ) were purchased from Fisher. The construction and characterization of the general fluorogenic THP substrate fTHP-4 and the MMP-2/MMP-9-specific fluorogenic THP substrate ␣1(V)436 -447 fTHP has been described previously (41,48,49).…”

Section: Methodsmentioning

confidence: 99%

“…The second assay was based on hydrolysis of fluorogenic substrates in solution by conditioned media (41,55). One volume of the appropriate fluorogenic substrate was added to each well in a 384-well plate.…”

Section: Type IV Collagen Induction Of Melanoma Cells 43506mentioning

confidence: 99%

“…The Gly-Phe-Hyp-Gly-Glu-Arg motif, in triple-helical conformation, has been shown to bind to the ␣ 2 ␤ 1 integrin (38 -40). This motif is found within type IV collagen at ␣1(IV)382-393 (39,41). 3 The type IV collagen ␣1(IV)1263-1277 sequence Gly-Val-Lys-Gly-Asp-Lys-Gly-AsnPro-Gly-Trp-Pro-Gly-Ala-Pro is bound by melanoma cell CD44 receptors in the chondroitin sulfate proteoglycan (CSPG) form (42)(43)(44).…”

mentioning

confidence: 99%

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Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by α2β1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen

Baronas-Lowell

Lauer‐Fields

Borgia³

et al. 2004

Journal of Biological Chemistry

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Tumor cell binding to components of the basement membrane is well known to trigger intracellular signaling pathways. Signaling ultimately results in the modulation of gene expression, facilitating metastasis. Type IV collagen is the major structural component of the basement membrane and is known to be a polyvalent ligand, possessing sequences bound by the ␣ 1 ␤ 1 , ␣ 2 ␤ 1 , and ␣ 3 ␤ 1 integrins, as well as cell surface proteoglycan receptors, such as CD44/chondroitin sulfate proteoglycan (CSPG). The role of ␣ 2 ␤ 1 integrin and CD44/CSPG receptor binding on human melanoma cell activation has been evaluated herein using triple-helical peptide ligands incorporating the ␣1(IV)382-393 and ␣1(IV)1263-1277 sequences, respectively. Gene expression and protein production of matrix metalloproteinases-1 (MMP-1), -2, -3, -13, and -14 were modulated with the ␣ 2 ␤ 1 -specific sequence, whereas the CD44-specific sequence yielded significant stimulation of MMP-8 and lower levels of modulation of MMP-1, -2, -13, and -14. Analysis of enzyme activity confirmed different melanoma cell proteolytic potentials based on engagement of either the ␣ 2 ␤ 1 integrin or CD44/CSPG. These results are indicative of specific activation events that tumor cells undergo upon binding to select regions of basement membrane collagen. Based on the present study, triple-helical peptide ligands provide a general approach for monitoring the regulation of proteolysis in cellular systems.Melanoma is one of the most rapidly increasing malignancies in the world in both young and old patients, with over 50,000 newly diagnosed patients each year (1). 1 Mortality from cancer is frequently due to metastasis, given that surgical excision of the primary tumor considerably enhances the prognosis of a patient and prolongs survival (2). Metastasis is a complex series of finely coordinated events that results in cancer cells circulating in lymph and blood vascular systems to invade remote tissues and establish secondary sites of tumor growth (3). Extravasation of the tumor cell into secondary tissues requires alterations in cellular behaviors, resulting from specific adhesion to components of the basement membrane. Tumor cells respond to each of the various components of the ECM, 2 including the collagens; noncollagenous glycoproteins, such as fibronectin and laminin; and proteoglycans, such as decorin and syndecan (4). These interactions are known to occur through several families of cell surface receptors, including the integrins and cell surface proteoglycans.Integrins are heterodimeric proteins composed of one ␣ and one ␤ subunit and are the best described of the cell surface adhesion molecules. To date, there are 18 different ␣ subunits and 8 distinct ␤ subunits identified that combine to form at least 24 heterodimers (5-7). Although the specific integrin expression profile can fluctuate with tumor type and stage of progression, highly metastatic melanoma cells are known to up-regulate expression of, and ␣ 6 ␤ 4 integrins while down-regulating the expression ...

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Section: Resultsmentioning

confidence: 83%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Type IV Collagen Induction Of Melanoma Cells 43506mentioning

confidence: 99%

mentioning

confidence: 99%

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Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by α2β1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen

Baronas-Lowell

Lauer‐Fields

Borgia³

et al. 2004

Journal of Biological Chemistry

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Metzincin Modulators

Minond¹

2015

Matrix Metalloproteinase Biology

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Solid‐phase synthesis, characterization, and cellular activities of collagen‐model Nanodiamond‐peptide conjugates

et al. 2015

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Nanodiamonds (NDs) have received considerable attention as potential drug delivery vehicles. NDs are small (~5 nm diameter), can be surface modified in a controllable fashion with a variety of functional groups, and have little observed toxicity in vitro and in vivo. However, most biomedical applications of NDs utilize surface adsorption of biomolecules, as opposed to covalent attachment. Covalent modification provides reliable and reproducible ND–biomolecule ratios, and alleviates concerns over biomolecule desorption prior to delivery. The present study has outlined methods for the efficient solid-phase conjugation of ND to peptides and characterization of ND–peptide conjugates. Utilizing collagen-derived peptides, the ND was found to support or even enhance the cell adhesion and viability activities of the conjugated sequence. Thus, NDs can be incorporated into peptides and proteins in a selective manner, where the presence of the ND could potentially enhance the in vivo activities of the biomolecule it is attached to.

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Selective Hydrolysis of Triple-helical Substrates by Matrix Metalloproteinase-2 and -9

Cited by 92 publications

References 52 publications

Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by α2β1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen

Differential Modulation of Human Melanoma Cell Metalloproteinase Expression by α2β1 Integrin and CD44 Triple-helical Ligands Derived from Type IV Collagen

Metzincin Modulators

Solid‐phase synthesis, characterization, and cellular activities of collagen‐model Nanodiamond‐peptide conjugates

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