Study of the inhibitory effects on invasion and metastasis of human squamous cell carcinoma by intensifying endothelial cell to cell adhesion

增强内皮细胞与细胞粘附抑制人鳞状细胞癌侵袭和转移的研究

• 批准号: 12671960
• 负责人: NAGAYASU Hiroki
• 金额: $ 1.47万
• 依托单位: Health Sciences University of Hokkaido, School of dentistry
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-12671960/
• 关键词: vascular endothelial cell; cell to cell adhesion; gap junction; connexin43; lung metastasis

Diisoprppyl,1,3-dithiol-2-y1idenemalonate(MT) is clinically used as a hepatoprotective agent. Because we noticed that the differentiation of cultured vascular endothelial cell, we have examined its effects on lung metastasis of the highly metastatic rat mammary carcinoma c-SST-2. MT was orally administered to syngenic SHR rats from 7 days before or after s. c.. inoculation of c-SST-2 cells to the end of the experiments. In the MT treated rats, pulumonary metastasis was markedly suppressed compared with the non-treated rats. In- the rats treated with MT for 19 days after i. v. inoculation of c-SST-2 cells, lung metastasis was also significantly suppressed. An in vitro invasion assay using a rat lung endothelial cell (RLE) monolayer revealed that pretreatment of the RLE with MT, but not c-SST-2 cells, significantly reduced the invasion of the RLE monolayer by c-SST-2 cells. An in vitro vascular permeability assay demonstrated that MT prevented the increase in permeability of the RLE monolayer by serum starvation. On the other hand, in vivo and in vitro growth, gelatinase production and adhesion to the RLE monolayer of c-SST-2 cells were not affected by NT treatment. Electronmicroscopical examination of the RLE monolayer treated with MT showed the development of gap junction Structure. A junction associated protein, cnnexin43 was also elevated at RLE treated with MT. These findings suggests that MT suppressed tumor metastasis by intensifying the cell-cell contact of endothelial cell, thus preventing tumor cells from invading vascular endothelium.

二异丙基,1,3-二硫醇-2-亚基丙二酸酯(MT)在临床上用作保肝剂。由于我们注意到培养的血管内皮细胞的分化，我们检查了其对高转移性大鼠乳腺癌c-SST-2肺转移的影响。从 s 之前或之后 7 天开始，对同源 SHR 大鼠口服 MT。 c..接种c-SST-2细胞至实验结束。在MT治疗的大鼠中，与未治疗的大鼠相比，肺转移明显受到抑制。在- i后用MT治疗19天的大鼠。 v.接种c-SST-2细胞，肺转移也被显着抑制。使用大鼠单层肺内皮细胞 (RLE) 进行的体外侵袭测定表明，用 MT（而不是 c-SST-2 细胞）预处理 RLE，可显着减少 c-SST-2 细胞对 RLE 单层的侵袭。体外血管通透性测定表明，MT 可以防止血清饥饿导致的 RLE 单层通透性增加。另一方面，c-SST-2 细胞的体内和体外生长、明胶酶产生以及对 RLE 单层的粘附不受 NT 处理的影响。用 MT 处理的 RLE 单层的电子显微镜检查显示间隙连接结构的发展。一种连接相关蛋白 cnnexin43 在用 MT 处理的 RLE 中也升高。这些发现表明，MT通过加强内皮细胞的细胞间接触来抑制肿瘤转移，从而阻止肿瘤细胞侵入血管内皮。

项目成果

中田大地, 柴田敏之, 永易裕樹, 他: "上皮成長因子EGFが退縮型ラット癌細胞ER-1の浸潤, 転移能に及ぼす影響 第3報, EGF長期間処理による酸化ストレスと遺伝的不安定性の誘導"日本口腔外科学会雑誌. 46(9). 511-518 (2000)

Daichi Nakata、Toshiyuki Shibata、Hiroki Nagayoshi 等人：“表皮生长因子 EGF 对消退大鼠癌细胞 ER-1 的侵袭和转移潜力的影响，第 3 部分，长期引起的氧化应激和遗传不稳定性的影响“EGF治疗”“指导”日本口腔颌面外科学会杂志. 46(9). 511-518 (2000)

H. Harada, K. Omura, H. Nggayasu, T. Yanagawa: "Pattern of occult cervical lymph node metastasis and neck dissection in In NO cases of squamous cell carcinoma or the tongue"J. J. O. M. S.. 46 (4). 191-195 (2000)

H. Harada、K. Omura、H. Nggayasu、T. Yanakawa：“鳞状细胞癌或舌癌病例中隐匿性颈部淋巴结转移和颈部清扫术的模式”J。

T.Shibata, H.Nagayasu, et al.: "Inhibitory effects of malotilate on in vitro invasion of lung endothelial cell monolayer by human oral squamous cell carcinoma cells"Tumor Biology. 21. 299-308 (2000)

T.Shibata、H.Nagayasu 等人：“马洛替酯对人口腔鳞状细胞癌细胞体外侵袭肺内皮细胞单层的抑制作用”肿瘤生物学。

原田浩之, 小村 健, 永易裕樹, 他: "舌扁平上皮癌NO症例における潜在性頸部リンパ節転移の様相と頸部郭清術式の検討"日本口腔外科学会雑誌. 46(4). 191-195 (2000)

Hiroyuki Harada、Ken Komura、Hiroki Nagayoshi 等：“舌鳞状细胞癌 NO 病例中隐匿性颈部淋巴结转移和颈部清扫技术”，日本口腔颌面外科杂志 46(4)。 191 -195 (2000)

T. Shhibata, H. Nagayasu et al.: "Inhibitory effects of malotilate on in vitro invasion of lung endothelial cell monolayer by human oral squamous cell carcinoma cells"Tumor Biology. 21. 299-308 (2000)

T. Shibata、H. Nagayasu 等人：“马洛替酯对人口腔鳞状细胞癌细胞体外侵袭肺内皮细胞单层的抑制作用”肿瘤生物学。