Metastatic mouse melanoma cells release collagen-gelatin degrading metalloproteinases as components of shed membrane vesicles

Zucker, Stanley; Wieman, Janine M.; Lysik, Rita M.; Wilkie, Dean; Ramamurthy, N.; Lane, Bernard

doi:10.1016/0304-4165(87)90091-2

Cited by 49 publications

(25 citation statements)

References 27 publications

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“…Little is known about the mechanisms of shed vesicle-enhanced cell invasiveness. 5,30 A pioneer study in this field by Poste and Nicolson 31 indicated that fusion of vesicles with the plasma membrane of tumor cells (obtained with agents causing membrane fusion) was required to increase their metastatic potential. It is therefore plausible that also in our case a direct interaction of the vesicles with the endothelial cells occur.…”

Section: Discussionmentioning

confidence: 99%

Shedding of the Matrix Metalloproteinases MMP-2, MMP-9, and MT1-MMP as Membrane Vesicle-Associated Components by Endothelial Cells

Taraboletti

D’Ascenzo

Borsotti

et al. 2002

The American Journal of Pathology

513

381

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Production of matrix-degrading proteases, particularly matrix metalloproteinases (MMPs), by endothelial cells is a critical event during angiogenesis, the process of vessel neoformation that occurs in normal and pathological conditions. MMPs are known to be highly regulated at the level of synthesis and activation, however, little is known about the regulation of MMP secretion by endothelial cells. We found that cultured human umbilical vein endothelial cells shed vesicles (300 to 600 nm) originating from localized areas of the cell plasma membrane, as revealed by ultrastructural analysis. Normal and reverse zymography, Western blot, and immunogold analyses of the vesicles showed two gelatinases, MMP-2 and MMP-9, in both the active and proenzyme forms, the MT1-MMP proenzyme located on the external side of the vesicle membrane and the two inhibitors TIMP-1 and TIMP-2. Serum and the angiogenic factors, fibroblast growth factor-2 and vascular endothelial growth factor, stimulated the shedding of MMPs as vesicle components. Shedding the vesicle was rapid, as it was already completed after 4 hours. Addition of shed vesicles to human umbilical vein endothelial cells resulted in autocrine stimulation of invasion through a layer of reconstituted basement membrane (Matrigel) and cord formation on Matrigel. We conclude that endothelial cells shed MMP-containing vesicles and this may be a mechanism for regulating focalized proteolytic activity vital to invasive and morphogenic events during angiogenesis. (Am J Pathol 2002, 160:673-680)

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Section: Discussionmentioning

confidence: 99%

Shedding of the Matrix Metalloproteinases MMP-2, MMP-9, and MT1-MMP as Membrane Vesicle-Associated Components by Endothelial Cells

Taraboletti

D’Ascenzo

Borsotti

et al. 2002

The American Journal of Pathology

513

381

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“…Its activity was also retained in membrane fractions after freezing and thawing and extraction with high-salt buffers. Additionally, the 170-kDa protease was found in the detergent extracts of 100,000 x g pellets derived from conditioned media, suggesting that the 170-kDa protease is released into the medium in membrane vesicles (23).…”

Section: Discussionmentioning

confidence: 99%

“…Serum-free conditioned media derived from cell culture were spun at low speed to remove floating cells and cell debris. Membranes from conditioned media were collected by centrifugation at 100,000 X g for 1 hr at 40C and then extracted in 2% octyl glucoside in Tris-buffered saline (TBS; 50 mM Tris HCl, pH 7.4/150 mM NaCl) as described (23) or extracted in 1% Triton X-114 in TBS and then partitioned into detergent and aqueous phases according to the previously described method (24). Total protein concentrations of various fractions were determined by BCA (bicinchoninic acid) assay (Pierce), using bovine serum albumin solutions as standards.…”

Section: Methodsmentioning

confidence: 99%

A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells.

Aoyama

Chen

1990

Proc. Natl. Acad. Sci. U.S.A.

112

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A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells (protease/plasma membrane/extracellular degradation/g au ase/iuvasion) ATSUKO AOYAMA AND WEN-TIEN CHEN* Department of Anatomy and Cell Biology, Georgetown University School of Medicine, Washington, DC 20007 Communicated by John M. Buchanan, July 31, 1990 ABSTRACT Malgnant spreading of cancer cells requires cell surface proteases that cleave the crosslinked collagenous matrix of connective tissues. From correlating the morphologically defined invasiveness of tumor cells with the presence of specific membrane-associated proteases, we have identified a malignant human melanoma cell line, LOX, that invades crosslinked gelatin films in vitro and contains uniquely a neutral 170-kDa gelatinase in the cell membrane. A similar gelatinase was found in membranes recovered from culture media conditioned with LOX. The 170-kDa gelatinase is a wheat germ agglutinin-binding protein. The proteolytic activity is maximal at neutral pH, enhanced by EDTA and dithiothreitol, inhibited by the cysteine protease inhibitors N-ethylmaleimide, HgCI2, and phenylmethylsulfonyl fluoride, and can bind to an organomercurial adsorbent, suggg that it is a neutral sulihydryl-sensitive protease. This 170-kDa gelatinase of LOX cells was not found in a control melanoma cell line, SK-MEL28, or in 32 other tumor cell lines that did not show extracellular gelatin degradation. Thus, we have identified a large membrane-bound protease that may be a specific marker molecule for melanoma cell invasiveness.

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“…Vesicle membranes carry most surface antigens expressed on the plasma membrane (30); however they originate from domains of the plasma membrane selectively enriched in membrane components including HLA class I molecules, ␤1 integrins, and membrane-bound matrix metalloproteinase-9 (31). Vesicle shedding has been implicated in cell migration and in tumor progression (32), a function that may be mediated by vesicle membrane-bound proteinases (28,31,(33)(34)(35)(36). Vesicles are also shed by several non-tumor cells (37,38) and have been reported to vehicle a variety of regulatory factors (25,26,29,30,36).…”

Section: Fibroblast Growth Factor-2 (Fgf-2)mentioning

confidence: 99%

Shedding of Membrane Vesicles Mediates Fibroblast Growth Factor-2 Release from Cells

Taverna

Ghersi

Ginestra

et al. 2003

Journal of Biological Chemistry

103

122

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Metastatic mouse melanoma cells release collagen-gelatin degrading metalloproteinases as components of shed membrane vesicles

Cited by 49 publications

References 27 publications

Shedding of the Matrix Metalloproteinases MMP-2, MMP-9, and MT1-MMP as Membrane Vesicle-Associated Components by Endothelial Cells

Shedding of the Matrix Metalloproteinases MMP-2, MMP-9, and MT1-MMP as Membrane Vesicle-Associated Components by Endothelial Cells

A 170-kDa membrane-bound protease is associated with the expression of invasiveness by human malignant melanoma cells.

Shedding of Membrane Vesicles Mediates Fibroblast Growth Factor-2 Release from Cells

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