Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration

Masahiro Kajita, Yoshifumi Itoh, Tadashige Chiba, Hidetoshi Mori, Akiko Okada, Hiroaki Kinoh, Motoharu Seiki

Research output: Contribution to journalArticle

559 Citations (Scopus)

Abstract

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 languageEnglish (US)
Pages (from-to)893-904
Number of pages12
JournalJournal of Cell Biology
Volume153
Issue number5
DOIs
StatePublished - May 25 2001
Externally publishedYes

Fingerprint

Matrix Metalloproteinase 14
Cell Movement
CD44 Antigens
Matrix Metalloproteinase Inhibitors
Tumor Cell Line
Extracellular Matrix
Neoplasms
Equipment and Supplies

Keywords

  • CD44
  • Invasion and metastasis
  • Metalloproteinase
  • Motility
  • MT-MMP

ASJC Scopus subject areas

  • Cell Biology

Cite this

Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. / Kajita, Masahiro; Itoh, Yoshifumi; Chiba, Tadashige; Mori, Hidetoshi; Okada, Akiko; Kinoh, Hiroaki; Seiki, Motoharu.

In: Journal of Cell Biology, Vol. 153, No. 5, 25.05.2001, p. 893-904.

Research output: Contribution to journalArticle

Kajita, M, Itoh, Y, Chiba, T, Mori, H, Okada, A, Kinoh, H & Seiki, M 2001, 'Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration', Journal of Cell Biology, vol. 153, no. 5, pp. 893-904. https://doi.org/10.1083/jcb.153.5.893
Kajita, Masahiro ; Itoh, Yoshifumi ; Chiba, Tadashige ; Mori, Hidetoshi ; Okada, Akiko ; Kinoh, Hiroaki ; Seiki, Motoharu. / Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration. In: Journal of Cell Biology. 2001 ; Vol. 153, No. 5. pp. 893-904.
@article{9f50732652424e1fb6657142d2bbda67,
title = "Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration",
abstract = "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.",
keywords = "CD44, Invasion and metastasis, Metalloproteinase, Motility, MT-MMP",
author = "Masahiro Kajita and Yoshifumi Itoh and Tadashige Chiba and Hidetoshi Mori and Akiko Okada and Hiroaki Kinoh and Motoharu Seiki",
year = "2001",
month = "5",
day = "25",
doi = "10.1083/jcb.153.5.893",
language = "English (US)",
volume = "153",
pages = "893--904",
journal = "Journal of Cell Biology",
issn = "0021-9525",
publisher = "Rockefeller University Press",
number = "5",

}

TY - JOUR

T1 - Membrane-type 1 matrix metalloproteinase cleaves CD44 and promotes cell migration

AU - Kajita, Masahiro

AU - Itoh, Yoshifumi

AU - Chiba, Tadashige

AU - Mori, Hidetoshi

AU - Okada, Akiko

AU - Kinoh, Hiroaki

AU - Seiki, Motoharu

PY - 2001/5/25

Y1 - 2001/5/25

N2 - 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.

AB - 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.

KW - CD44

KW - Invasion and metastasis

KW - Metalloproteinase

KW - Motility

KW - MT-MMP

UR - http://www.scopus.com/inward/record.url?scp=0035947766&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0035947766&partnerID=8YFLogxK

U2 - 10.1083/jcb.153.5.893

DO - 10.1083/jcb.153.5.893

M3 - Article

C2 - 11381077

AN - SCOPUS:0035947766

VL - 153

SP - 893

EP - 904

JO - Journal of Cell Biology

JF - Journal of Cell Biology

SN - 0021-9525

IS - 5

ER -