Experimental studies of invasive and proliferative activity of oral squamous cell carcinoma

口腔鳞状细胞癌侵袭和增殖活性的实验研究

• 批准号: 11470432
• 负责人: YAMAMOTO Etsuhide
• 金额: $ 5.57万
• 依托单位: Kanazawa University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2001
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-11470432/
• 关键词: Oral Squamous cell carcinoma; Invasion; Metastasis; Motility factor; Adbesion molecule; Proteinase; 接着因子; 基質分解能; 口腔癌; 運動因子; 扁平上皮癌; 増殖

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 sub classified 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.

自1978年以来，我们一直在研究癌症侵袭模式作为口腔鳞状细胞癌患者的重要预后因素。 Jakobsson提出的4级侵袭方式又分为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类癌症材料、DMBA诱导的舌癌以及使用3个细胞系的体外和体内侵袭模型； OCS-20（3 级）、OSC-19（4C 级）和 HOC-313（4D 级）。在免疫染色的人类癌症材料中，侵袭方式的等级越高，基底膜的连续性越差，细胞间的粘附性越差。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。在细胞运动测定中，HOC-313显示出最大的运动性（自分泌运动因子；AMF）。在包埋胶原蛋白凝胶的 3T3 成纤维细胞上培养的细胞系显示出与其来源相似的侵袭模式。其中，即使没有包埋成纤维细胞，也只有HOC-313表现出侵袭性。在DMBA诱导的舌癌中，观察从Gr.1到Gr.4C的侵袭模式。 OSC-20和OSC-19原位植入裸鼠舌头中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。在最近的研究中，细胞选择的 TSU (Gr.4D) 在组织学与起源相似的 SCID 小鼠中产生了致命的致瘤性。该分级系统也通过免疫组织化学和实验证明是合理的。

项目成果

Kawashiri, S., Kojima, K., Yamamoto, E., et al.: "FEffects of chemotherapy on invasion and metastasis of oral cavity cancer in mice"Head & Neck. 23. 764-771 (2001)

Kawashiri, S.、Kojima, K.、Yamamoto, E. 等人：“化疗对小鼠口腔癌侵袭和转移的影响”Head

Kawashiri S, Tanaka A, Yamamoto E, et al.: "Expression of the active type gelatinase of the oral squamous cell carcinoma"Oral Oncology, Proc. of the 7th International Congress on Oral Cancer. 7. 529-532 (2001)

Kawashiri S、Tanaka A、Yamamoto E 等人：“口腔鳞状细胞癌活性型明胶酶的表达”Oral Oncology，Proc。

Kawashiri S., Kumagai S., Yamamoto E., et al.: "Reproduclion of occult metastasis of head and neck cancer in nude mice"Clinical & Experimental Metastasis. 17. 277-282 (1999)

Kawashiri S.、Kumagai S.、Yamamoto E.等人：“裸鼠头颈癌隐匿性转移的再现”临床

Kawashiri, S., Tanaika, A., Yamamoto, E., Tachikawa, T, Speight, PM: "Expression of the active type gelatin ease of the oral squamous cell carcinoma"Oral Oncology Proc. Of the 7th International Congress on Oral Cancer. 7. 529-532 (2001)

Kawashiri, S.、Tanaika, A.、Yamamoto, E.、Tachikawa, T、Speight, PM：“口腔鳞状细胞癌活性型明胶的表达”Oral Oncology Proc。

Tanaka A, Kawashiri S, Yamamoto E, et al.: "Pathological relationship between basement membrane degradation and mode of invasion for oral sguamous cell carcinoma"Oral Oncology, Proc. of the 7th International Congress on Oral Cancer. 7. 571-574 (2001)

Tanaka A、Kawashiri S、Yamamoto E 等人：“口腔鳞状细胞癌基底膜退化与侵袭模式之间的病理关系”口腔肿瘤学，Proc。