title: Matrix metalloproteinase-9 and vascular endothelial growth factor: a possible link in adult T-cell leukaemia cell invasion.
abstract: Plasma from a total of 57 patients with adult T-cell leukaemia (ATL) (acute ATL, 39 patients; lymphoma ATL, one patient; chronic ATL, 15 patients; smouldering ATL, two patients) and 20 healthy controls was analysed for the presence of type IV gelatinase activity with clinical features. A significant elevation of plasma matrix metalloproteinase-9 (MMP-9) was observed in some ATL patients, particularly in the patients with malignant cell infiltration. MMP-9 was found to be secreted into the conditioned medium from all ATL cell lines examined. Moreover, the corresponding mRNA was detectable both in all ATL cell lines examined and in the majority of primary acute ATL cells, indicating that ATL cells are capable of synthesizing and secreting MMP-9. We previously demonstrated that a high incidence of ATL cell infiltration was closely related to a high plasma level of vascular endothelial growth factor (VEGF) produced by ATL cells themselves. This present study showed that the presence of increased plasma MMP-9 was closely associated with elevated plasma VEGF in ATL patients. Furthermore, we showed that both increased plasma MMP-9 and VEGF were significantly related to high ATL cell infiltration. All these findings strongly suggest that MMP-9 and VEGF act co-operatively in the process of ATL cell invasion.
authors.affiliation: Department of Biochemistry, Molecular Medicine Unit, Atomic Disease Institute, Nagasaki University School of Medicine, Nagasaki University, Nagasaki, Japan. lantisth@net.nagasaki-u.ac.jp
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Hayashibara
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Yamada
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Onimaru
authors.forename: Chizuko
authors.initials: C
authors.lastname: Tsutsumi
authors.forename: Susumu
authors.initials: S
authors.lastname: Nakayama
authors.forename: Naoki
authors.initials: N
authors.lastname: Mori
authors.forename: Takayuki
authors.initials: T
authors.lastname: Miyanishi
authors.forename: Shimeru
authors.initials: S
authors.lastname: Kamihira
authors.forename: Masao
authors.initials: M
authors.lastname: Tomonaga
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Maita
mesh_terms: D000208:Acute Disease; D000328:Adult; D016022:Case-Control Studies; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel / Q000379:methods; D016228:Endothelial Growth Factors / Q000097:blood*; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D015461:Leukemia, Prolymphocytic, T-Cell / Q000097:blood / Q000473:pathology; D015458:Leukemia, T-Cell / Q000097:blood* / Q000473:pathology; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000097:blood / Q000473:pathology; D017254:Leukemic Infiltration; D008222:Lymphokines / Q000097:blood*; D016399:Lymphoma, T-Cell / Q000097:blood / Q000473:pathology; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D008222:Lymphokines; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D020780:Matrix Metalloproteinase 9