Open AccessHeparanase and tumor invasion patterns in human oral squamous cell carcinoma xenografts
Author(s) -
Kurokawa Hitoshi,
Katsube Kenichi,
Podyma Katarzyna A.,
Ikuta Minoru,
Iseki Hachirou,
Nakajima Motowo,
Akashi Takumi,
Omura Ken,
Takagi Minoru,
Yanagishita Masaki
Publication year - 2003
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2003.tb01433.x
Subject(s) - heparanase , heparan sulfate , cancer , cancer cell , perlecan , glycosaminoglycan , biology , extracellular matrix , cell , basement membrane , pathology , cancer research , metastasis , immunohistochemistry , chemistry , immunology , microbiology and biotechnology , medicine , biochemistry , genetics
The role of heparanase, an endo‐β‐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 pro‐teoglycan 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. (Cancer Sci 2003; 94: 277–285)