Expression and activity of matrix metalloproteinase 2 and 9 in human trophoblasts.
Indiscriminate invasion upon the endometrium by normal trophoblasts is strictly regulated unlike that by choriocarcinoma cells. In this study, we focused on the activity of matrix metalloproteinase (MMP)-2 and MMP-9 as parameters of invasion in normal human placenta. In situ hybridization (ISH), immunohistochemical staining (IH) and film in situ zymography (FIZ) were performed to identify cells having MMP-2 or MMP-9 expression and activity. Purified cytotrophoblasts (CTs) were used to examine the expression and activity of MMP-2 and MMP-9, and their invasive ability. In first trimester placental tissue, the MMP-2 expression was observed in extravillous trophoblasts (EVTs), and MMP-9 mainly in villous cytotrophoblasts (VCTs). FIZ revealed marked gelatinase activity in the EVTs which MMP-2 expression was observed in. In full-term placental tissue, the MMP-2 expressions was observed in the EVTs similar to that in first trimester, whereas the gelatinase activity in these cells was decreased or completely lost. Using purified CTs, the gelatinase activity was marked in early CTs, but not term CTs. Invasive ability of early CTs was inhibited by tissue inhibitor of metalloproteinase (TIMP)-2 and MMP-2 antibody in a dose dependent manner. These suggests that the invasive ability of trophoblasts may be regulated by the enzyme activity of gelatinases, especially MMP-2.
Isaka
K
K
Department of Obstetrics and Gynecology, Tokyo Medical University, 6-7-1 Nishi-Shinjuku, Japan. isaka@tokyo-med.ac.jp
Usuda
S
S
Ito
H
H
Sagawa
Y
Y
Nakamura
H
H
Nishi
H
H
Suzuki
Y
Y
Li
Y F
YF
Takayama
M
M
D000328:Adult; D019138:Antibodies, Blocking / Q000494:pharmacology; D002822:Choriocarcinoma / Q000201:enzymology / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D009361:Neoplasm Invasiveness / Q000473:pathology; D016133:Polymerase Chain Reaction; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D011263:Pregnancy Trimester, Third; D012333:RNA, Messenger / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000494:pharmacology; D014327:Trophoblasts / Q000201:enzymology*; D014407:Tumor Cells, Cultured / Q000201:enzymology / Q000473:pathology
D019138:Antibodies, Blocking; D012333:RNA, Messenger; D019716:Tissue Inhibitor of Metalloproteinase-2; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9