Biological Significance of HB-EGF Expression at Cell-Cell Contact Sites in Progression of Ovarian Cancer

细胞-细胞接触位点 HB-EGF 表达在卵巢癌进展中的生物学意义

基本信息

批准号：
16591667
负责人：
MIYAMOTO Shingo
金额：
$ 2.3万
依托单位：
Fukuoka University (2005)Kyushu University (2004)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16591667/
关键词：
HB-EGF Ovarian Cancer EGFR Transactivation ADAM Family Tumor Growth LPA インテグリン EGFRリガンド

项目摘要

Ovarian cancer, which is one of the gynecologic cancers, has been recognized as a cancer with extremely poor prognosis, although the chemotherapy using carboplatin and paclitaxel has provided the improvement of 5 year's survival rates. Up to date, many targeting therapies for ovarian cancer have been developed. Unfortunately, however, these therapies are not effective for patients with ovarian cancer. It is urgent that a novel targeting therapy for ovarian cancer is established.Ascites from patients with ovarian cancer are considered to be a rich source of growth factor activity for ovarian cancer cells. Recent biochemical analysis has revealed that LPA (Lysophosphatidic acid) id one possible ovarian cancer activating factor candidate. In principle, LPA and other GPCR (G protein-coupled receptor) ligands induce proteolytic cleavage of the extracellular domain (ectodomain shedding) of EGFR (epidermal growth factor receptor) ligands at the cell surface. The secreted EGF family ligands th … More en activate EGFR on ligation. Thus LPA signals and the EGFR system are thought to be closely connected.The aim of this study is to search for novel effective therapies targets and further establish the targeting therapy for ovarian cancer. First, we studied the expression of EGFR ligands in patients with ovarian cancer We found that among the EGFR ligands, HB-EGF gene expression in cancerous tissues and HB-EGF protein levels in patients' ascites fluid were significantly elevated, compared to the expression of other EGFR ligands. In addition to these results, tumor formation of ovarian cancer cells (SKOV3 and RMG-1) was completely blocked by pro-HB-EGF gene RNA interference and pro-HB-EGF gene with an uncleavable mutant. According to these evidences, HB-EGF is recognized as a promising target for ovarian cancer The administration of CRM197, a specific HB-EGF inhibitor, abrogated the tumor growth of ovarian cancer cells in nude mice. CRM197, which is a non-toxic mutant form of diphtheria toxin, can be safely administered for cancer patients The administration of CRM197 would allow us to improve clinical prognosis of ovarian cancer. Less

卵巢癌是妇科癌症之一，虽然卡铂和紫杉醇的化疗已经提高了5年的生存率，但迄今为止，许多针对卵巢癌的靶向治疗已被认为是预后极差的癌症。然而不幸的是，这些疗法对卵巢癌患者无效，迫切需要建立一种针对卵巢癌患者腹水的新型靶向疗法。被认为是卵巢癌细胞生长因子活性的丰富来源。最近的生化分析表明，LPA（溶血磷脂酸）是一种可能的卵巢癌激活因子候选物。原则上，LPA 和其他 GPCR（G 蛋白偶联受体）配体。诱导细胞表面 EGFR（表皮生长因子受体）配体的胞外域（胞外域脱落）的蛋白水解裂解分泌型 EGF 家族。因此，LPA 信号和 EGFR 系统被认为是密切相关的。本研究的目的是寻找新的有效治疗靶点，并进一步建立卵巢癌的靶向治疗。研究了卵巢癌患者EGFR配体的表达情况，我们发现EGFR配体中，癌组织中的HB-EGF基因表达量和患者腹水中的HB-EGF蛋白水平显着升高，与其他 EGFR 配体的表达相比，除了这些结果外，卵巢癌细胞（SKOV3 和 RMG-1）的肿瘤形成被 pro-HB-EGF 基因 RNA 干扰和不可切割的 pro-HB-EGF 基因完全阻断。根据这些证据，HB-EGF 被认为是卵巢癌的一个有希望的靶点。 CRM197（一种特异性 HB-EGF 抑制剂）的给药可抑制裸卵巢癌细胞的肿瘤生长。 CRM197是一种无毒的白喉毒素突变体，可以安全地用于癌症患者。CRM197的施用将使我们能够改善卵巢癌的临床预后。

项目成果

期刊论文数量（62）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Invasive potency related to RCAS1 expression in uterine cancer.

子宫癌中与 RCAS1 表达相关的侵袭能力。

DOI：
发表时间：
2005
期刊：
Gynecologic Oncology 99
影响因子：
0
作者：
Kenzo Sonoda;Shingo Miyamoto et al.
通讯作者：
Shingo Miyamoto et al.

Investigation on the molecular regulation of Extravillous Trophoblast differentiation in placentogenesis

胎盘发生过程中绒毛外滋养细胞分化的分子调控研究

DOI：
发表时间：
2004
期刊：
Proceedings of 14th Fukuoka international symposium of Perinatal Medicine
影响因子：
0
作者：
Yamamasu S;Iwanaga N;Tachibana D;et al.;福嶋恒太郎;Fukushima K et al.;Fukushima K et al.;Fukushima K et al.
通讯作者：
Fukushima K et al.

Clinical significance of heparin-binding EGF (epidermal growth factor)-like growth factor and ADAM (a disintegrin and metalloprotease) 17 expression in human ovarian cancer.

人卵巢癌中肝素结合 EGF（表皮生长因子）样生长因子和 ADAM（解整合素和金属蛋白酶）17 表达的临床意义。