title: Heparanase and tumor invasion patterns in human oral squamous cell carcinoma xenografts.
abstract: The role of heparanase, an endo-beta-glucuronidase specifically degrading heparan sulfate (HS) glycosaminoglycans, in the mechanism of cancer cell invasion was investigated. Three human oral squamous cell carcinoma (SCC) cell lines (i.e., HSC-2, HSC-3 and LMF4), exhibiting various degrees of invasiveness to their surrounding tissues, were xenografted to the tongue of SCID mice in order to establish experimental cancer foci. Cancer cells and their surrounding tissues were examined for the expression of heparanase mRNA by an in situ hybridization technique, and for various basement membrane (BM)-associated molecules (i.e., perlecan, laminins and type IV collagen) by immunohistochemical procedures. BM structures surrounding cancer tissues were also examined by electron microscopy. Increasing levels of heparanase mRNA expression were observed with the progression of cancer invasiveness, as manifested by the destruction of BM structures. Enhanced heparanase enzyme activities in cancer tissues with more invasive properties were demonstrated by the disappearance of HS glycosaminoglycans in the face of retained HS proteoglycan core proteins. These results demonstrated a positive correlation between the heparanase enzyme activities and the invasiveness of human oral SCC. The roles of heparanase in cancer cell invasion were not precisely clarified by the present morphological study, but the enhanced heparanase activity in an early phase of BM destruction by cancer cells suggested the participation of this enzyme from the early phase of cancer invasion.
authors.affiliation: Oral Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Tokyo Medical and Dental University.
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kurokawa
authors.forename: Ken-ichi
authors.initials: K
authors.lastname: Katsube
authors.forename: Katarzyna A
authors.initials: KA
authors.lastname: Podyma
authors.forename: Minoru
authors.initials: M
authors.lastname: Ikuta
authors.forename: Hachirou
authors.initials: H
authors.lastname: Iseki
authors.forename: Motowo
authors.initials: M
authors.lastname: Nakajima
authors.forename: Takumi
authors.initials: T
authors.lastname: Akashi
authors.forename: Ken
authors.initials: K
authors.lastname: Omura
authors.forename: Minoru
authors.initials: M
authors.lastname: Takagi
authors.forename: Masaki
authors.initials: M
authors.lastname: Yanagishita
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D005966:Glucuronidase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007150:Immunohistochemistry; D051379:Mice; D016513:Mice, SCID; D009062:Mouth Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D009361:Neoplasm Invasiveness; D012333:RNA, Messenger / Q000235:genetics; D014062:Tongue Neoplasms / Q000201:enzymology / Q000235:genetics / Q000473:pathology; D014158:Transcription, Genetic; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D000099175:Heparanase
chemical_list: D005966:Glucuronidase; D012333:RNA, Messenger; D000099175:Heparanase