Overexpression of MT1-MMP is insufficient to increase experimental liver metastasis of human colon cancer cells.
The expression and activation of matrix metalloproteinases (MMPs) by tumor cells is correlated with invasive and metastatic potential. The purpose of this study was to examine the impact of increased membrane type 1 matrix metalloproteinase (MT1-MMP) expression on liver metastatic potential utilizing human colorectal cancer (CRC) cell lines. Three human CRC cell lines, DLD1, HCT116 and HT29, were stably transfected with the MT1-MMP cDNA, and experimental liver metastasis was established by injecting the cells into the spleens of nude mice. Reverse transcription-polymerase chain reaction (RT-PCR) confirmed increased expression of MT1-MMP mRNA in the stable tranfectants. In vitro analysis by gelatin zymography and morphological survey demonstrated that MT1-MMP transfectants displayed a matured gelatinolytic activity and invasive properties when cultured in 3D collagen gel, indicating that transduced MT1-MMP cDNA was functional. Although there was no difference in cell proliferation rate between MT1-MMP overexpressing cells and the Mock control cells, in vivo experiments indicated that the liver metastatic ability was not affected by MT1-MMP overexpression. Our findings indicated that conditional MT1-MMP overexpression was insufficient to increase experimental liver metastasis, suggesting a more complicated mechanism may be involved in the activation and regulation of MMPs cascades in vivo.
Yamamoto
Hirofumi
H
Department of Surgery, Gastroenterological Surgery, Graduate School of Medicine, Osaka University, 2-2 Yamada-oka, Osaka 565-0871, Japan. kobunyam@surg2.med.osaka-u.ac.jp
Noura
Shingo
S
Okami
Jiro
J
Uemura
Mamoru
M
Takemasa
Ichiro
I
Ikeda
Masataka
M
Ishii
Hideshi
H
Sekimoto
Mitsugu
M
Matsuura
Nariaki
N
Monden
Morito
M
Mori
Masaki
M
D000818:Animals; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D003110:Colonic Neoplasms / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D015870:Gene Expression; D045325:HCT116 Cells; D019073:HT29 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000556:secondary*; D053511:Matrix Metalloproteinase 14 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D014162:Transfection
C507086:MMP14 protein, human; D053511:Matrix Metalloproteinase 14