Establishment of recipient cells for oncogene detection and analysis of transformation-associated cell surface antigen expression

建立用于癌基因检测和转化相关细胞表面抗原表达分析的受体细胞

• 批准号: 61570180
• 负责人: SATO Noriyuki
• 金额: $ 1.6万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1988
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-61570180/
• 关键词: oncogenes; WFB; tumor antigens; natural killer target structures; heat shock protein; natural killer target structures; 癌遺伝子; NK標的分子; 熱ショック蛋白; 癌抗原; トランスフォーメーション; 単クローン抗体; NK活性; 標的分子; DNAトランスフェクション

The detail of anti-tumor surveillance mechanisms by the hosts is still unknown. Surface phenotypes and the ontogeny of NK cells have been widely studied, and there is considerable heterogeneity among NK cell populations. However, little is known about the target structures of tumor cells that are recognized by NK cells. It is also essential to investigate how these structures could be associated with the cell transformation process.We have demonstrated two different candidates of the NK target molecules, namely 86 kd and 62 kd protein composed of a single polypeptide chain. These were defined by monoclonal antibodies (mabs), #109 and #061, respectively, and were highly associated with the activated H-ras oncogene-induced transformation of WKA rat fetus-derived fibroblast WFB. It is also strongly suggested that the expression of 86 kd and not that of the 62 kd molecule was enhanced on nontumorigenic WFD cells which were stimulated by PDGF. The data suggest that these two different molecules are directly involved in the NK-target cell interactions as the target strucutres. These molecules may play an important role in the antitumor surveillance by the hosts.On the other hand, another mab #067 recognizing 67 kd single polypeptide reacted selectively with W31 but not with w14 and other EKras-WFB or PyMt-WFB transformants as well as parental WFB. The expression of this antigen was enhanced on W31 by treatment with heat, superoxide and cAMP or cholera toxin. Furthermore, it was induced by these treatment on W14 and other EKras WFB transformants that did not show constitutively this antigen under the regular culture conditions. These data suggested that this antigen is a novel heat-inducible molecule, and might be a tumor specific antigen of WFB cells.

宿主抗肿瘤监视机制的细节仍不清楚。 NK细胞的表面表型和个体发育已被广泛研究，并且NK细胞群体之间存在相当大的异质性。然而，人们对 NK 细胞识别的肿瘤细胞的靶结构知之甚少。研究这些结构如何与细胞转化过程相关也很重要。我们已经证明了 NK 靶分子的两种不同候选者，即由单个多肽链组成的 86 kd 和 62 kd 蛋白质。这些分别由单克隆抗体 (mab) #109 和 #061 定义，并且与激活的 H-ras 癌基因诱导的 WKA 大鼠胎儿来源的成纤维细胞 WFB 转化高度相关。还强烈表明，在受PDGF刺激的非致瘤性WFD细胞上，86kd分子的表达增强，而不是62kd分子的表达增强。数据表明，这两种不同的分子作为靶结构直接参与 NK-靶细胞相互作用。这些分子可能在宿主的抗肿瘤监视中发挥重要作用。 另一方面，另一种识别 67 kd 单多肽的 mab #067 选择性地与 W31 反应，但不与 w14 和其他 EKras-WFB 或 PyMt-WFB 转化体以及亲本 WFB 反应。通过热、超氧化物和 cAMP 或霍乱毒素处理，W31 上该抗原的表达得到增强。此外，它是通过对 W14 和其他 EKras WFB 转化体进行这些处理而诱导的，这些转化体在常规培养条件下不组成型地显示该抗原。这些数据表明该抗原是一种新型热诱导分子，并且可能是WFB细胞的肿瘤特异性抗原。

项目成果

林秀男、山村雄一: "最新免疫研究法" 医学書院, 357 (1988)

Hideo Hayashi、Yuichi Yamamura：“最新免疫学研究方法”Igaku Shoin，357（1988）

浜岡利之、橋本嘉幸: "癌と免疫" メジカルビュー社, 1-176 (1987)

Toshiyuki Hamaoka、Yoshiyuki Hashimoto：“癌症与免疫”Medical View Publishing，1-176 (1987)

Sato,N.;Yagihashi,A.;Torigoe,T.;Okubo,M.;Konno,A.;Takahashi,N.;yamashita,T.;Fujinaga,K.;Kazumaki,N.;Kikuchi,K.: Cancer Research. 48. 2798-2804 (1988)

佐藤，N.；八木桥，A.；鸟越，T.；大久保，M.；绀野，A.；高桥，N.；山下，T.；藤永，K.；一牧，N.；菊池，K.：

Sato, N.: Cancer Res.47. 3147-3135 (1987)

佐藤，N.：癌症研究 47。

Yagihashi, A.: Cancer Res.(1988)

八木桥，A.：癌症研究（1988）