Experimental studies of invasion and metastasis activity of oral squamous cell carcinoma

自1978年以来，我们一直在研究口腔鳞状细胞癌患者的重要预后因素癌症的侵袭方式。Jakobsson提出的4级侵犯模式又分为4C级（索状型）和4D级（弥漫型）。本研究的目的是通过免疫组织化学和实验阐明这种改良的侵袭模式分级系统。使用的材料和方法是人癌材料、DMBA诱导的舌癌和使用3种细胞系的体外和体内侵袭模型; OCS-20（Gr.3）、OSC-19（Gr.4C）和HOC-313（Gr.4D）。在免疫组化染色的人癌组织中，浸润方式分级越高，基底膜越不连续，细胞间粘附越少。大多数弥漫性浸润癌（Gr.4C和4D）共表达膜型基质金属蛋白酶和基质金属蛋白酶-2。在细胞运动性测定中，HOC-313显示最大的运动性（自分泌运动因子; AMF）。在3 T3成纤维细胞包埋的胶原凝胶上培养的细胞系显示出与其来源相似的侵袭模式。其中只有HOC-313在成纤维细胞未包埋的情况下也表现出侵袭性。DMBA诱发的舌癌细胞的侵袭方式为Gr.1 ~ Gr.4C。原位植入裸鼠舌中的OSC-20和OSC-19生长并转移至淋巴结。它们的组织学外观与起源相似。HOC-313在基质胶的支持下暂时生长了几个月。最近的研究表明，细胞选择性大津单位（Gr.4D）在SCID小鼠中产生了致死性致瘤性，其组织学与起源相似。这种分级系统也被证明是化学和实验合理的。

Since 1978, 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, DMBA induced tongue cancer 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 basement membrane was, and the less intercellular adhesion was. Majority of diffuse invasive cancers(Gr.4C and 4D) co-expressed membrane type-matrix metalloproteinase and matrix metalloprotenase-2. In cell motility assay, HOC-313 showed the greatest motility (autocrine motility factor ; AMF). Cell lines cultured on 3T3 fibroblast-embedded collagen gels showed similar invasion pattern to their origin. Among them, only HOC-313 showed invasion even if fibroblast was not embedded. In DMBA induced tongue cancer, the mode of invasion were observed from Gr.1 to Gr.4C. 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 TSU (Gr.4D) produced lethal tumorgenicity in SCID mouse with similar histology to the origin. This grading system was also proven immunohistochemically and experimentally justifiable.