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Background <p>Membrane type 1 matrix metalloproteinase/matrix metalloproteinase 14 (MT1-MMP-MMP-14) is associated with various stages of cancer, particularly metastasis. The intracellular cytoplasmic domain of MMP-14 has recently been recognized for the ability to regulate cellular behaviors, particularly under conditions of low pH and/or hypoxia, which can occur within the tumor microenvironment.</p> Purpose <p>The present work has focused on developing tools to evaluate changes that occur to the cytoplasmic domain of MMP-14 under the aforementioned conditions.</p> Methods <p>Variants of the cytoplasmic domain containing posttranslational modifications have been synthesized and characterized, and flow cytometric analysis has been examined as an approach to quantify extracellular and intracellular MMP-14 in pancreatic cancer cell lines under normal and hypoxic conditions.</p> Results <p>Four variants of the MMP-14 cytoplasmic domain were synthesized, where the variants contained no modifications, phosphorylation, palmitoylation, or monoubiquitination. The structure of each variant was impacted when the pH was lowered. For quantification of intracellular MMP-14 flow cytometry was effective under both normoxic and hypoxic conditions.</p> Conclusion <p>The synthesized cytoplasmic domain peptides can be used to raise antibodies for flow cytometric evaluation of the state of the cytoplasmic domain in cell spheroids under tumor microenvironment (low pH, hypoxic) conditions.</p>

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Development of Tools for Evaluating the Matrix Metalloproteinase 14 Cytoplasmic Domain in the Tumor Microenvironment

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年1月8日

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  • Chandani Singh,
  • Jessica Frank,
  • Kathryn Martin,
  • Nihasika Gopi,
  • Dorota Tokmina-Roszyk,
  • Gregg B. Fields

摘要

Background

Membrane type 1 matrix metalloproteinase/matrix metalloproteinase 14 (MT1-MMP-MMP-14) is associated with various stages of cancer, particularly metastasis. The intracellular cytoplasmic domain of MMP-14 has recently been recognized for the ability to regulate cellular behaviors, particularly under conditions of low pH and/or hypoxia, which can occur within the tumor microenvironment.

Purpose

The present work has focused on developing tools to evaluate changes that occur to the cytoplasmic domain of MMP-14 under the aforementioned conditions.

Methods

Variants of the cytoplasmic domain containing posttranslational modifications have been synthesized and characterized, and flow cytometric analysis has been examined as an approach to quantify extracellular and intracellular MMP-14 in pancreatic cancer cell lines under normal and hypoxic conditions.

Results

Four variants of the MMP-14 cytoplasmic domain were synthesized, where the variants contained no modifications, phosphorylation, palmitoylation, or monoubiquitination. The structure of each variant was impacted when the pH was lowered. For quantification of intracellular MMP-14 flow cytometry was effective under both normoxic and hypoxic conditions.

Conclusion

The synthesized cytoplasmic domain peptides can be used to raise antibodies for flow cytometric evaluation of the state of the cytoplasmic domain in cell spheroids under tumor microenvironment (low pH, hypoxic) conditions.