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 language | English (US) |
|---|---|
| Pages (from-to) | 893-904 |
| Number of pages | 12 |
| Journal | Journal of Cell Biology |
| Volume | 153 |
| Issue number | 5 |
| DOIs | |
| State | Published - May 25 2001 |
| Externally published | Yes |
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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 journal › Article
}
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 -