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

自1978年以来，我们一直在研究癌症的侵袭方式作为口腔鳞状细胞癌患者预后的重要因素。Jakobsson提出的侵袭模式4级又分为4C级（绳状型）和4D级（弥漫性）。本研究的目的是免疫组织化学和实验阐明这种改进的分级系统的入侵模式。采用的材料和方法为人癌材料、DMBA诱导舌癌及3种细胞系体外和体内侵袭模型；OCS-20 （Gr.3）、OSC-19 （Gr.4C）和HOC-313 （Gr.4D）。在免疫染色的人肿瘤材料中，侵袭方式越高，基底膜的连续性越差，细胞间黏附越少。大多数弥漫性浸润性癌症(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。在细胞运动试验中，HOC-313表现出最大的运动性（自分泌运动因子；AMF）。在3T3成纤维细胞包埋的胶原凝胶上培养的细胞系表现出与其来源相似的侵袭模式。其中，即使未包埋成纤维细胞，也只有HOC-313表现出侵袭性。在DMBA诱导的舌癌中，浸润模式从Gr.1到Gr.4C。OSC-20和OSC-19原位植入裸鼠舌内生长并转移至淋巴结。其组织学表现与起源相似。HOC-313在matrigel的支持下暂时增长了几个月。在最近的研究中，细胞选择的TSU （Gr.4D）在与起源组织学相似的SCID小鼠中产生致死性肿瘤。该分级系统也被免疫组织化学和实验证明是合理的。

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.