Investigation the mechanisms on invasion and metastasisof oral squamous cell carcinoma

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We have been studying the mode of cancer invasion as the important prognostic factor in patients with oral squamous cell cancer. Grade 4 of mode of invasion proposed by Jakobsson was subclassified into grades 4C (Cord-like type) and 4D (Diffuse type). The purpose of this study is to immunohistochemically and experimentally elucidate this modified grading system for the mode of invasion. Materials and methods used are human cancer materials and in vitro and in vivo invasion model by using 3 cell lines; OCS-20 (Gr.3), OSC-19 (Gr. 4C) and HOC-313 (Gr. 4D). In immunostained human cancer materials, the higher the grade of the mode of invasion was, the less continuous the type 4 collagen was, and the less E-cadherin was. Majority of diffuse invasive cancers (Gr. 4C and 4D) expressed MMPs and HIF-1. In cell invasion assay, HOC-313 showed the greatestmotility (AMF). Cell lines cultured on 3T3 fibroblast-embedded collagen gels showed similar invasion pattern to their origin. Among them, only HOC-313 showed invasion evenif fibroblast was not embedded. OSC-20 and OSC-19 implanted orthotopically in the tongue of nude mice grew and metastasized to lymph nodes. Their histologic appearance was similar to that of the origin. HOC-313 grew temporarily for several months by support of matrigel. In recent study, cell selected OLC-01 (Gr.4D) produced lethal tumorgenicity in nude mouse with similar histology to the origin.