Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

Migratory cells including invasive tumor cells frequently express CD44, a major receptor for hyaluronan and membrane-type 1 matrix metalloproteinase (MT1-MMP) that degrades extracellular matrix at the pericellular region. In this study, we demonstrate that MT1-MMP acts as a processing enzyme for CD44H, releasing it into the medium as a soluble 70-kD fragment. Furthermore, this processing event stimulates cell motility; however, expression of either CD44H or MT1-MMP alone did not stimulate cell motility. Coexpression of MT1-MMP and mutant CD44H lacking the MT1-MMP-processing site did not result in shedding and did not promote cell migration, suggesting that the processing of CD44H by MT1-MMP is critical in the migratory stimulation. Moreover, expression of the mutant CD44H inhibited the cell migration promoted by CD44H and MT1-MMP in a dominant-negative manner. The pancreatic tumor cell line, MIA PaCa-2, was found to shed the 70-kD CD44H fragment in a MT1-MMP-dependent manner. Expression of the mutant CD44H in the cells as well as MMP inhibitor treatment effectively inhibited the migration, suggesting that MIA PaCa-2 cells indeed use the CD44H and MT1-MMP as migratory devices. These findings revealed a novel interaction of the two molecules that have each been implicated in tumor cell migration and invasion.

Original publication

DOI

10.1083/jcb.153.5.893

Type

Journal article

Journal

The Journal of cell biology

Publication Date

05/2001

Volume

153

Pages

893 - 904

Addresses

Department of Cancer Cell Research, Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokane-dai, Minato-ku, Tokyo 108-8639, Japan.

Keywords

Tumor Cells, Cultured, Extracellular Matrix, Animals, Humans, Mice, Pancreatic Neoplasms, Neoplasm Invasiveness, Sulfones, Thiophenes, Metalloendopeptidases, Leucine, Phenylalanine, Antigens, CD44, Plant Proteins, Tissue Inhibitor of Metalloproteinase-1, Tissue Inhibitor of Metalloproteinase-2, Trypsin Inhibitors, Ligands, Cell Movement, Cell Size, Protein Processing, Post-Translational, Sequence Deletion, Amino Acid Sequence, Genes, Dominant, Solubility, Molecular Sequence Data, Matrix Metalloproteinases, Membrane-Associated, Matrix Metalloproteinase 14, alpha-Amylases