title: Expression pattern alterations of the serine protease HtrA1 in normal human placental tissues and in gestational trophoblastic diseases.
abstract: HtrA1 is a secreted protein which behaves as a molecular chaperone at low temperatures and as a serine protease at high temperatures. When the placenta escapes the normal growth control mechanisms, which are present during normal pregnancy, it may develop trophoblastic diseases, such as hydatidiform mole and choriocarcinoma. The aim of the study is to investigate the expression of HtrA1 in these gestational trophoblastic diseases and evaluate whether different HtrA1 expression might be associated with increasingly severe forms of disease. We used immunohistochemistry to assess the expression of HtrA1 in normal human placenta, hydatidiform mole (partial and complete) and choriocarcinoma. In addition to that we used the western blotting technique to quantify HtrA1 immunoreaction in normal human placentas. The most striking finding of our investigation is the decrease in immunostaining of this protease with increasing severity of gestational trophoblastic disease. For instance, in partial and complete moles HtrA1 is weakly expressed in the trophoblast. Moreover, absence of immunoreaction for HtrA1 is observable in the choriocarcinoma cells. In conclusion, we suggest that HtrA1 may play an important role in the pathogenesis and progression of hydatidiform moles and choriocarcinomas, and that HtrA1 may play an important role during the normal development of the placenta, as well as in trophoblastic diseases.
authors.affiliation: Department of Molecular Pathology and Innovative Therapies, Faculty of Medicine, Polytechnic University of Marche, Ancona, Italy. d.marzioni@univpm.it
authors.forename: Daniela
authors.initials: D
authors.lastname: Marzioni
authors.forename: Alexia
authors.initials: A
authors.lastname: Quaranta
authors.forename: Teresa
authors.initials: T
authors.lastname: Lorenzi
authors.forename: Manrico
authors.initials: M
authors.lastname: Morroni
authors.forename: Caterina
authors.initials: C
authors.lastname: Crescimanno
authors.forename: Michele
authors.initials: M
authors.lastname: De Nictolis
authors.forename: Paolo
authors.initials: P
authors.lastname: Toti
authors.forename: Giovanni
authors.initials: G
authors.lastname: Muzzonigro
authors.forename: Alfonso
authors.initials: A
authors.lastname: Baldi
authors.forename: Antonio
authors.initials: A
authors.lastname: De Luca
authors.forename: Mario
authors.initials: M
authors.lastname: Castellucci
mesh_terms: D000595:Amino Acid Sequence; D016022:Case-Control Studies; D002822:Choriocarcinoma / Q000378:metabolism / Q000473:pathology; D005260:Female; D005865:Gestational Age; D031901:Gestational Trophoblastic Disease / Q000378:metabolism* / Q000473:pathology; D005982:Glutathione Transferase / Q000378:metabolism; D000074289:High-Temperature Requirement A Serine Peptidase 1; D006801:Humans; D006828:Hydatidiform Mole / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D008969:Molecular Sequence Data; D010920:Placenta / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D011247:Pregnancy; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism; D012697:Serine Endopeptidases / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D011993:Recombinant Fusion Proteins; D005982:Glutathione Transferase; D000074289:High-Temperature Requirement A Serine Peptidase 1; C474012:HTRA1 protein, human; D012697:Serine Endopeptidases