title: Protein Z/protein Z-dependent protease inhibitor system in loco in human gastric cancer.
abstract: In gastric cancer, hemostatic system components contribute to cancer progression, as activation of factor X (FX) was observed. The protein Z (PZ)/protein Z-dependent protease inhibitor (ZPI) complex inhibits factor Xa proteolytic activity. The purpose of this study was to determine the distribution of ZPI and PZ in relation to FX, and prothrombin fragment (F1 + 2), a standard marker for blood coagulation activation, in human gastric cancer tissue. ABC procedures and a double staining method employed polyclonal antibodies against PZ, FX, and F1 + 2 and a monoclonal antibody against ZPI. In situ hybridization (ISH) methods employed biotin-labeled 25-nucleotide single-stranded DNA probes directed to either PZ or ZPI mRNAs. FX and components of PZ/ZPI coagulation inhibitory system were observed in cancer cells. F1 + 2 was observed in gastric cancer cells as well. Double staining studies revealed FX/PZ, FX/ZPI, and PZ/ZPI co-localization on gastric cancer cells. ISH studies demonstrated the presence of PZ mRNA and ZPI mRNA in gastric cancer cells indicating induced synthesis of these proteins. The co-localization of PZ/ZPI and FX in gastric cancer cells indicates in loco that these proteins may play a role in anticoagulant events at the tumor tissue.
authors.affiliation: Department of Oncology, Medical University, 12 Ogrodowa St., Bialystok, Poland, ewa.sierko@iq.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sierko
authors.forename: Marek Z
authors.initials: MZ
authors.lastname: Wojtukiewicz
authors.forename: Lech
authors.initials: L
authors.lastname: Zimnoch
authors.forename: Piotr
authors.initials: P
authors.lastname: Tokajuk
authors.forename: Krystyna
authors.initials: K
authors.lastname: Ostrowska-Cichocka
authors.forename: Walter
authors.initials: W
authors.lastname: Kisiel
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D001777:Blood Coagulation; D001798:Blood Proteins / Q000235:genetics* / Q000378:metabolism; D018450:Disease Progression; D015951:Factor Xa / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D010446:Peptide Fragments / Q000235:genetics / Q000378:metabolism; D011498:Protein Precursors / Q000235:genetics / Q000378:metabolism; D011516:Prothrombin / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics* / Q000378:metabolism; D015843:Serpins / Q000235:genetics* / Q000378:metabolism; D013274:Stomach Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology
chemical_list: D001798:Blood Proteins; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C416370:SERPINA10 protein, human; D015843:Serpins; C026080:plasma protein Z; C029733:prothrombin fragment 1; C044183:prothrombin fragment 2; D011516:Prothrombin; D015951:Factor Xa