Differential Expression Patterns of a Disintegrin and Metalloproteinase With Thrombospondin Motifs (ADAMTS) -1, -4, -5, and -14 in Human Placenta and Gestational Trophoblastic Diseases

Abstract

Context.-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.Design.-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.

Polymorphisms in the precursor microRNAs and aflatoxin B1‐related hepatocellular carcinoma

“…Functionally, it is responsible for the degradation of aggrecan [37][38][39]. Increasing evidence has shown that the dysregulation of ADAMTS4 expression involves in the tumorigenesis of some tumor, such as melanoma, head and neck cancer, Ewing's sarcoma, and choriocarcinoma [40][41][42][43][44]. In this study, we accomplished a gene expression profile and silico analysis and found that the rs28599926 polymorphism significantly downregulated ADAMTS4 expression.…”

A new biological marker candidate in female reproductive system diseases: Matrix metalloproteinase with thrombospondin motifs (ADAMTS)

“…For successful placentation, the transformation cytotrophoblasts into intermediate trophoblast and the invasion of these cells into maternal tissues are needed (31). During placenta formation, extravillous trophoblasts lose their cell-cell interactions and secrete various proteases, including ADAMTS1.…”

“…In ADAMTS1 knockout mice, it was observed that the pregnancy rate declined (33). ADAMTS4 and -5 are expressed at very high levels, especially in the first-trimester placenta and are responsible for maternal tissue invasion (31). ADAMTS5 presence in first-trimester decidual endometrial tissue was determined.…”

Single‐nucleotide polymorphisms in the coding region of a disintegrin and metalloproteinase with thrombospondin motifs 4 and hepatocellular carcinoma: A retrospective case‐control study

“…Human ADAMTS4 (also known as ADMP‐1 , ADAMTS‐2 , or ADAMTS‐4 ), a major member of ADAMTS family genes, is an important aggrecanase involving in collagen maturation, matrix degradation, organogenesis, and blood coagulation . In the past several decades, the epidemiological and clinicopathological studies have shown that the dysregulation of ADAMTS4 expression and function may involve in the process of some tumors, including head and neck cancer, melanoma, choriocarcinoma, and Ewing's sarcoma . Demircan et al investigated the expression of ADAMTS4 mRNA in primary head and neck squamous cell carcinoma with and without metastasis by quantitative real time polymerase chain reaction technique and found that higher expression was in the metastatic tumor tissues.…”