What question did this study set out to answer?

Identify novel extracellular substrates of matrix metalloproteinase-9 (MMP-9) using a label-free quantitative degradomics approach in metastatic prostate cancer cells.

July 2, 2008Molecular & Cellular ProteomicsOpen Access

Novel MMP-9 Substrates in Cancer Cells Revealed by a Label-free Quantitative Proteomics Approach

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Authors

DXDanmei XuTongji Hospital NSNaoko SuenagaTokyo Medical University MEMariola J. EdelmannUniversity of Florida

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Implication

In vitro proteomics study reveals novel direct MMP-9 substrates in metastatic prostate cancer cells, highlighting potential molecular drivers of tumor metastasis.

Key Points

Identify novel extracellular substrates of matrix metalloproteinase-9 (MMP-9) using a label-free quantitative degradomics approach in metastatic prostate cancer cells.
Knocked down MMP-9 expression in human metastatic prostate cancer cells (PC-3ML) via RNA interference and collected conditioned medium alongside parental cells.
Profiled secretomes using label-free ultraperformance LC-ESI-high/low collision energy mass spectrometry to quantify differences in protein levels.
Validated candidate substrates using immunoblotting, tested direct cleavage via in vitro incubations with recombinant MMP-9, and sequenced cleavage sites.
Identified over 200 secreted proteins, of which 69 demonstrated significant alterations in abundance (>±2-fold) upon MMP-9 depletion.
Immunoblotting confirmed altered levels of six candidates: amyloid-beta precursor protein, collagen VI, leukemia inhibitory factor, neuropilin-1, PCDGF, and protease nexin-1 (PN-1).
Demonstrated direct MMP-9-mediated degradation of PN-1 and leukemia inhibitory factor in vitro, mapped PN-1 cleavage sites, and revealed preferential cleavage of collagen VI terminal globular regions over helical domains.

Cite This Study

Xu et al. (2008) studied this question.

synapsesocial.com/papers/6a719b90febe604dd70a31ac https://doi.org/10.1074/mcp.m800095-mcp200

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Implication

In vitro proteomics study reveals novel direct MMP-9 substrates in metastatic prostate cancer cells, highlighting potential molecular drivers of tumor metastasis.

Novel MMP-9 Substrates in Cancer Cells Revealed by a Label-free Quantitative Proteomics Approach

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Implication

Key Points

Cite This Study

Novel MMP-9 Substrates in Cancer Cells Revealed by a Label-free Quantitative Proteomics Approach

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Implication

Key Points

Cite This Study

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