The role of MT2-MMP in cancer progression.
The role of MT2-MMP in cancer progression remains to be elucidated in spite of many reports on MT1-MMP. Using a human fibrosarcoma cell, HT1080 and a human gastric cancer cell, TMK-1, endogenous expression of MT1-MMP or MT2-MMP was suppressed by siRNA induction to examine the influence of cancer progression in vitro and in vivo. In HT1080 cells, positive both in MT1-MMP and MT2-MMP, the migration as well as the invasion was impaired by MT1-MMP or MT2-MMP suppression. Also cell proliferation in three dimensional (3D) condition was inhibited by MT1-MMP or MT2-MMP suppression and tumor growth in the nude mice transplanted with tumor cells were reduced either MT1-MMP or MT2-MMP suppression with a prolongation of survival time in vivo. MT2-MMP suppression induces more inhibitory effects on 3D proliferation and in vivo tumor growth than MT1-MMP. On the other hand, TMK-1 cells, negative in MT1-MMP and MMP-2 but positive in MT2-MMP, all the migratory, invasive, and 3D proliferative activities in TMK-1 are decreased only by MT2-MMP suppression. These results indicate MT2-MMP might be involved in the cancer progression more than or equal to MT1-MMP independently of MMP-2 and MT1-MMP.
Ito
Emiko
E
Department of Molecular Pathology, Osaka University, Suita, Japan.
Yana
Ikuo
I
Fujita
Chisato
C
Irifune
Aiko
A
Takeda
Maki
M
Madachi
Ayako
A
Mori
Seiji
S
Hamada
Yoshinosuke
Y
Kawaguchi
Naomasa
N
Matsuura
Nariaki
N
D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D018450:Disease Progression; D006801:Humans; D053517:Matrix Metalloproteinase 15 / Q000235:genetics / Q000378:metabolism*; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology*; D034622:RNA Interference; D034741:RNA, Small Interfering / Q000235:genetics
D034741:RNA, Small Interfering; D053517:Matrix Metalloproteinase 15