Induction of NHC antigens of trophoblastic cells using some cytokines and its application to the immunotherapy in choriocarcinoma

某些细胞因子诱导滋养层细胞NHC抗原及其在绒毛膜癌免疫治疗中的应用

• 批准号: 03670778
• 负责人: GOTO Setsuko
• 金额: $ 1.41万
• 依托单位: Nagoya 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: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670778/
• 关键词: Choriocarcinoma; DNA polymorphism; VNTR; MHC; EGF; Autocrine mechanism; Metastasis; Collagenase activity; Interferon; Zymography; 絨毛癌細胞; コラゲナーゼ活性; DNA 多型性; EGFR; 免疫療法

(1) In three cases of choriocarcinoma, genetic loci including a variable number of tandem repeat regions were amplified by the polymerase chain reaction method on DNA from three established cell lines and from lymphocytes of patients and their husbands to identify the responsible pregeacy. In case 1, tumor cells was found to be parental origin and derived from the pregnancy with full-term fetal death. In case 2 and 3, tumor cells were probable androgenetic origin respectively, and were derived from the pregnancy with compiete hydatidiform mole. We also conducted the restriction fragment length polymorphism method using one case samples, and it confirmed the results based on the polymerase chain reaction method producted patterns. All nine cases of hydatidiform mole and three cased of invasive mole were of androgenetic origin.(2) In examination for the presence of Epidermal Growth Factor (EGF)/Epidermal GRowth Factor REceptor (EGFR) using EGF and 1251-EGF binding assay in conditioned medium. Specific EGF binding sites were observed in these five cell lines. Particularlily, in one cell line, NaUCC-4, we assessed the significance of EGF/EGFR autocrine mechanism.Immunocytochemical studies of NaUCC-4 cells showed that EGF and EGFR proteins were detected. The addition of monoclonal antibodies (mAbs) against EGF or EGFR inhibited 3H-thymidine incorporation and hCG production dose dependently. These results suggested that EGF might function as an autocrine growth factor in this choriocarcinoma cell line. (3) Choriocarcinoma cells showed high 72kDa geratinase activity, which suggested a role for the enzyme in vascular metasrasis. Studies on use of r IFN-B to inhibit metastasis of choriocarcinoma via supression of geratinase production are warranted.

(1)在3例绒毛膜癌中，通过聚合酶链反应方法对来自3个已建立的细胞系和患者及其丈夫的淋巴细胞的DNA扩增包括可变数目的串联重复区域的遗传位点，以确定负责的妊娠。在病例1中，发现肿瘤细胞是亲本来源，并且来自足月胎儿死亡的妊娠。例2和例3的肿瘤细胞可能分别为雄激素源性肿瘤，均来源于妊娠合并完全性葡萄胎。同时对一例病例进行了限制性片段长度多态性分析，并根据聚合酶链反应的结果进行了验证。9例葡萄胎和3例侵蚀性葡萄胎均为雄激素源性。(2)在条件培养基中使用EGF和1251-EGF结合试验检查表皮生长因子（EGF）/表皮生长因子受体（EGFR）的存在。在这五种细胞系中观察到特异性EGF结合位点。特别是在NaUCC-4细胞系中，我们研究了EGF/EGFR自分泌机制的意义。加入抗EGF或EGFR的单克隆抗体（mAb）可剂量依赖性地抑制3 H-胸苷掺入和hCG产生。这些结果表明，表皮生长因子可能作为一种自分泌生长因子在该绒毛膜癌细胞系。(3)绒毛膜癌细胞表现出高72 kDa的geratinase活性，这表明血管转移的酶的作用。因此，有必要研究r IFN-B通过抑制Geratinase的产生来抑制绒毛膜癌的转移。

项目成果

KATO N.,ET AL: "SUPRESSION OF GELATINASE PRODUCTION WITH DECREASED INVASIVENESS OF CHORIOCARCINOMA CELLS BY HUMAN RECOMBINANT INTERFERON-BETA" JAPANESE CANCER RESEARCH IN PRESS.

加藤 N. 等人：“人重组干扰素-β 抑制明胶酶的产生，降低绒毛膜癌细胞的侵袭性”日本癌症研究出版社。

Itsuko Suzuki et al.: "Pregnancy after Chemotherapy for Trophoblastic Diseases and Psychosomatic Development in the Progeny" Asia-Oceania Journal of Obstetrics and Gynecology. 19. 407-415 (1993)

Itsuko Suzuki 等人：“滋养细胞疾病化疗后怀孕和后代心身发育”亚洲-大洋洲妇产科杂志。

SUZUKI T.,GOTO S.,ET AL: "IDENTIFICATION OF THE PREGNANCY RESPONSIBLE FOR GESTATIONAL TROPHOBLASTIC DIS4EASE BY DNA ANALYSIS" OBSTETRICS AND GYNECOLOGY. 82. 629-654 (1993)

SUZUKI T.、GOTO S.、ET AL：“通过 DNA 分析识别妊娠期滋养细胞疾病的责任”妇产科。

Takanobu Suzuki et al.: "IDENTIFICATION OF THE PREGNANCY RESPONSIBLE FOR TROPHOBLASTIC DISEASE BY DNA ANALYSIS" Obstetrics and Gynecolpgy. 82. 629-634 (1993)

Takanobu Suzuki 等人：“通过 DNA 分析识别妊娠负责滋养细胞疾病”妇产科。

Noriko Kato et al.: "Supression of gelatinase with decreased invasiveness of choriocarcinoma cells by human recombinant interferon-beta" Japanese Journal of Cancer Research. (in press).

Noriko Kato 等人：“人重组干扰素-β 抑制明胶酶，降低绒毛膜癌细胞的侵袭性”，《日本癌症研究杂志》。