Related Experiment Videos
Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration
1Department of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.
The Journal of Cell Biology
|May 31, 2001
Summary
Matrix metalloproteinase-1 (MT1-MMP) processes CD44H, releasing a soluble fragment that stimulates tumor cell migration. This interaction is crucial for cell motility and invasion, particularly in pancreatic cancer cells.
Area of Science:
- Molecular Biology
- Cell Biology
- Cancer Research
Background:
- Migratory cells, including invasive tumor cells, often express CD44, a receptor for hyaluronan and membrane-type 1 matrix metalloproteinase (MT1-MMP).
- MT1-MMP degrades extracellular matrix, facilitating cell movement and invasion.
Purpose of the Study:
- To investigate the role of MT1-MMP in processing CD44H and its impact on cell motility.
- To elucidate the mechanism by which CD44H and MT1-MMP interaction contributes to tumor cell migration and invasion.
Main Methods:
- Investigated the enzymatic activity of MT1-MMP on CD44H.
- Utilized mutant CD44H lacking the MT1-MMP processing site to assess its role in cell migration.
- Examined the expression and shedding of CD44H fragments in pancreatic tumor cell lines (MIA PaCa-2).
Main Results:
- MT1-MMP processes CD44H, releasing a soluble 70-kD fragment that stimulates cell motility.
- Coexpression of MT1-MMP and CD44H is required for migratory stimulation; neither molecule alone is sufficient.
- A mutant CD44H lacking the MT1-MMP processing site inhibited cell migration, indicating the critical role of MT1-MMP-mediated processing.
Conclusions:
- The processing of CD44H by MT1-MMP is essential for stimulating cell migration.
- Pancreatic tumor cells utilize the CD44H-MT1-MMP axis as a migratory device.
- This study reveals a novel interaction between CD44H and MT1-MMP in promoting tumor cell migration and invasion.