Differential expression patterns of a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS) -1, -4, -5, and -14 in human placenta and gestational trophoblastic diseases

Arch Pathol Lab Med. 2014 May;138(5):643-50. doi: 10.5858/arpa.2012-0227-OA.

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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / biosynthesis*
  • ADAMTS Proteins
  • ADAMTS1 Protein
  • ADAMTS4 Protein
  • ADAMTS5 Protein
  • Adult
  • Choriocarcinoma / metabolism
  • Choriocarcinoma / pathology
  • Female
  • Gene Expression Regulation
  • Gene Expression Regulation, Neoplastic
  • Gestational Trophoblastic Disease / metabolism*
  • Gestational Trophoblastic Disease / pathology
  • Humans
  • Hydatidiform Mole, Invasive / metabolism
  • Hydatidiform Mole, Invasive / pathology
  • Middle Aged
  • Placenta / metabolism*
  • Placenta / pathology
  • Pregnancy
  • Procollagen N-Endopeptidase / biosynthesis*
  • Uterine Neoplasms / metabolism
  • Uterine Neoplasms / pathology

Substances

  • ADAM Proteins
  • ADAMTS Proteins
  • ADAMTS1 Protein
  • ADAMTS1 protein, human
  • ADAMTS14 protein, human
  • ADAMTS5 Protein
  • ADAMTS5 protein, human
  • Procollagen N-Endopeptidase
  • ADAMTS4 Protein
  • ADAMTS4 protein, human