Kurokawa Hitoshi, Katsube Ken-ichi, Podyma Katarzyna A, Ikuta Minoru, Iseki Hachirou, Nakajima Motowo, Akashi Takumi, Omura Ken, Takagi Minoru, Yanagishita Masaki
Oral Surgery, Department of Oral Restitution, Division of Oral Health Sciences, Tokyo Medical and Dental University.
Cancer Sci. 2003 Mar;94(3):277-85. doi: 10.1111/j.1349-7006.2003.tb01433.x.
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.
研究了乙酰肝素酶（一种特异性降解硫酸乙酰肝素（HS）糖胺聚糖的内切β-葡萄糖醛酸酶）在癌细胞侵袭机制中的作用。将三种对周围组织表现出不同程度侵袭性的人口腔鳞状细胞癌（SCC）细胞系（即HSC-2、HSC-3和LMF4）接种到SCID小鼠的舌部，以建立实验性癌灶。通过原位杂交技术检测癌细胞及其周围组织中乙酰肝素酶mRNA的表达，并通过免疫组织化学方法检测各种基底膜（BM）相关分子（即基底膜聚糖、层粘连蛋白和IV型胶原）。还通过电子显微镜检查癌组织周围的BM结构。随着癌侵袭性的进展，观察到乙酰肝素酶mRNA表达水平升高，表现为BM结构的破坏。面对保留的HS蛋白聚糖核心蛋白时HS糖胺聚糖的消失证明了具有更强侵袭性的癌组织中乙酰肝素酶活性增强。这些结果证明了乙酰肝素酶活性与人类口腔SCC侵袭性之间呈正相关。本形态学研究未确切阐明乙酰肝素酶在癌细胞侵袭中的作用，但癌细胞在BM破坏早期乙酰肝素酶活性增强提示该酶在癌侵袭早期就参与其中。
