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Effects of fibroblast inhibitor on invasion and metastasis of oral cancer

成纤维细胞抑制剂对口腔癌侵袭和转移的影响

基本信息

批准号：
21K10039
负责人：
野口夏代
金额：
$ 2.66万
依托单位：
Kanazawa University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2021
资助国家：
日本
起止时间：
2021-04-01 至 2024-03-31
项目状态：
已结题

项目摘要

本研究では口腔扁平上皮癌における線維芽細胞像増殖抑制剤が腫瘍の増殖や浸潤、転移にどのような影響を及ぼすか調査することを目的としている。2021年度は線維芽細胞像増殖抑制剤のピルフェニドンについて検討を行い、腫瘍の大きさの縮小ならびに腫瘍周囲の線維化の減少を認め、癌細胞の浸潤や転移を抑制する効果を有するものと考えられた。そこで2022年度は間質性肺炎の治療薬として使用されているニンテダニブの効果を検討するため、癌細胞の浸潤過程における間質のCancer associate fibroblast (CAF)および血管・リンパ管新生について調査し、癌細胞が移植後に生着、増殖、浸潤、進展する際に腫瘍間質および血管・リンパ管がどの様に変化するか、腫瘍の浸潤や進展との関連を詳細に調査した。また、免疫組織化学的にCAFのマーカーであるαSMA抗体、FGF抗体、血管内皮細胞のマーカーであるCD34抗体、リンパ管のマーカーであるD2-40 抗体を用いてそれぞれ染色し、癌細胞の進展との関係について観察した。口腔扁平上皮癌細胞株については昨年と同様に高悪性で高率にリンパ節転移を認めるOSC-19細胞株を使用した。これらを解析し、ニンテダニブの腫瘍間質と血管、リンパ管の癌細胞浸潤や転移に対する効果を検討した。その結果、癌細胞が増殖する際には、周囲の間質に線維芽細胞の造成と血管やリンパ管の増生が観察された。癌細胞の浸潤部線維芽細胞は浸潤の先進部でαSMA陽性の線維芽細胞が認められCAFが存在していた。一方、ニンテダニブを投与した腫瘍では、腫瘍の大きさは小さく、腫瘍周囲の線維化の減少と、血管、リンパ管数の減少を認めた。また、所属リンパ節転移を有意に抑制していた。以上より、線維芽細胞増殖抑制剤のニンテダニブは腫瘍の増殖抑制ならびに、癌細胞の浸潤や転移を抑制する効果を有するものと考えられた。

In this study, the cell lines of oral flat epithelial carcinoma were examined by cell culture, cell growth inhibition, cell growth inhibition, cell proliferation, cell proliferation, cell proliferation, In the year 2021, the number of cell lines in line maintenance sprouts is similar to that of colonization suppression. the results show that there are significant changes in the growth inhibition rate, cell cycle, cell cycle and cell migration in 2021. In 2022, the treatment of infectious pneumonia caused by the use of cancer cells in the treatment of viral pneumonia in the year 2022. The results showed that the cancer cells were born, colonized, impregnated after transplantation, and the cancer cells were born, colonized, impregnated, cultured, cultured and implanted after transplantation. The results showed that the cancer cells were born, colonized, immersed, and infected. In order to improve the quality of the blood vessels, the blood vessels are not allowed to change, and the blood vessels are not affected. Immunocytochemistry showed that CAF antibody, FGF antibody, vascular endothelial cell antibody, CD34 antibody, vascular endothelial cell antibody, D2-40 antibody were stained by immunohisto-chemical staining, and cancer cells were detected by immunostaining. The cell line of oral flat epithelial carcinoma was the same as that of oral flat epithelial carcinoma last year. The high rate of sexual infection was the same as that of OSC-19 cell line. The blood vessels, the tubes, the cancer, the cell infiltration, the transfer, the results, the blood vessels, the cancer, the blood vessels, the cancer, the cell infiltration, the cell infiltration, the tumor, the blood vessels, the cancer cells, the blood vessels, the cancer cells, the blood vessels, the blood vessels, the cancer cells, the blood vessels, the cancer cells, the blood vessels, the blood vessels, the cancer cells, the blood vessels, the The results showed that the proliferation of cancer cells and the maintenance of germ cells in the peripheral blood cells resulted in the growth of blood vessels. Cancer cell immersion cell line maintenance germ cell immersion cell line alpha SMA sex line maintenance germ cell cycle cell cycle CAF gene expression. On the other hand, the number of blood vessels and vessels is very small, and the number of blood vessels and vessels is very small. The owner is interested in suppressing the situation. The above cell colonization inhibition, linear maintenance bud colonization inhibition, cancer cell infiltration inhibition, tumor cell migration inhibition, cancer cell proliferation inhibition, cancer cell migration inhibition, cancer cell proliferation inhibition, cancer cell migration inhibition, cancer cell migration inhibition, tumor cell proliferation inhibition, cancer cell migration inhibition, cancer cell migration, tumor cell migration, cell proliferation, cell proliferation, cell migration, cell proliferation, cell proliferation, cell migration, cell