Differential expression patterns of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) -1, -4, -5, and -14 in human placenta and gestational trophoblastic diseases.
BACKGROUND
The ability of intermediate trophoblasts to invade maternal tissue during placentation depends on how well they can degrade the extracellular matrix. Invasion into the extracellular matrix requires many complex proteases. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) is a novel family of secreted metalloproteinases. The ADAMTS-1, -4, -5, and -14 subtypes are known to be expressed in human placenta, but little is understood about their expression patterns.


OBJECTIVE
To examine the expression patterns of ADAMTS-1, -4, -5, and -14 in specific human placenta cell types during gestation and in gestational trophoblastic diseases.


METHODS
Placental tissues were obtained from 25 pregnant women and 21 cases of gestational trophoblastic diseases (10 early complete moles, 3 placental site trophoblastic tumors, 4 invasive moles, and 4 choriocarcinomas). The expression of the 4 ADAMTS was analyzed by immunohistochemistry.


RESULTS
ADAMTS-1, -4, -5, and -14 were differentially expressed by the human placenta throughout gestation in a time-specific and cell type-specific manner, as well as in gestational trophoblastic diseases. ADAMTS-1 showed gradually strong staining intensity in gestational trophoblastic diseases according to the invasive potential but showed consistent strong intensity throughout normal placenta. ADAMTS-4 and ADAMTS-5 exhibited higher and restricted expression in first-trimester intermediate trophoblasts. They also exhibited comparably strong expression in gestational trophoblastic diseases. However, ADAMTS-14 expression remained unchanged throughout gestation.


CONCLUSIONS
The restricted expression pattern of ADAMTS-4 and ADAMTS-5 and their increased expression in gestational trophoblastic diseases suggest that these 2 ADAMTS subtypes are associated with a biological phenotype of trophoblasts involved in human placentation and the development of gestational trophoblastic diseases.
From the Department of Pathology, Asan Medical Center (Drs S-Y. Lee, C. J. Kim, K-R. Kim, and C-S. Park), and Asan Institute for Life Science (Ms H-S. Lee and Dr Gil), University of Ulsan, College of Medicine, Seoul, and Department of Pathology, University of Ajou, College of Medicine, Ajou University Hospital, Su-won (Dr Y-H. Lee), Korea.
So-Young
SY
Lee
Hyang-Sin
HS
Lee
Minchan
M
Gil
Chong Jai
CJ
Kim
Yong-Hee
YH
Lee
Kyu-Rae
KR
Kim
Chan-Sik
CS
Park
D051722:ADAM Proteins / Q000096:biosynthesis*; D000071096:ADAMTS Proteins; D000071097:ADAMTS1 Protein; D000071121:ADAMTS4 Protein; D000071116:ADAMTS5 Protein; D000328:Adult; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D005786:Gene Expression Regulation; D015972:Gene Expression Regulation, Neoplastic; D031901:Gestational Trophoblastic Disease / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D002820:Hydatidiform Mole, Invasive / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D010920:Placenta / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011348:Procollagen N-Endopeptidase / Q000096:biosynthesis*; D014594:Uterine Neoplasms / Q000378:metabolism / Q000473:pathology
D051722:ADAM Proteins; D000071096:ADAMTS Proteins; D000071097:ADAMTS1 Protein; C103859:ADAMTS1 protein, human; C447060:ADAMTS14 protein, human; D000071116:ADAMTS5 Protein; C121532:ADAMTS5 protein, human; D011348:Procollagen N-Endopeptidase; D000071121:ADAMTS4 Protein; C000603918:ADAMTS4 protein, human