Your browser doesn't support javascript.
loading
A NOTCH1 Mutation Found in a Newly Established Ovarian Cancer Cell Line (FDOVL) Promotes Lymph Node Metastasis in Ovarian Cancer.
Jiang, Wei; Ouyang, Xueyan; Jiang, Chunjuan; Yin, Lina; Yao, Qianlan; Pei, Xuan; Ji, Zhaodong; Li, Ming; Song, Shaoli; Yang, Wentao; Huang, Shenglin; Yang, Huijuan; Shan, Boer.
Afiliação
  • Jiang W; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Ouyang X; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Jiang C; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Yin L; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Yao Q; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Pei X; Department of Nuclear Medicine, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Ji Z; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Li M; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Song S; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Yang W; Department of Pathology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Huang S; Department of Gynecological Oncology, Fudan University Shanghai Cancer Center, Fudan University, Shanghai 200032, China.
  • Yang H; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
  • Shan B; Department of Clinical Laboratory, Huashan Hospital, Fudan University, Shanghai 200040, China.
Int J Mol Sci ; 24(6)2023 Mar 07.
Article em En | MEDLINE | ID: mdl-36982170
ABSTRACT
Peritoneal implantation and lymph node metastasis have different driving mechanisms in ovarian cancer. Elucidating the underlying mechanism of lymph node metastasis is important for treatment outcomes. A new cell line, FDOVL, was established from a metastatic lymph node of a patient with primary platinum-resistant ovarian cancer and was then characterized. The effect of NOTCH1-p.C702fs mutation and NOTCH1 inhibitor on migration was evaluated in vitro and in vivo. Ten paired primary sites and metastatic lymph nodes were analyzed by RNA sequencing. The FDOVL cell line with serious karyotype abnormalities could be stably passaged and could be used to generated xenografts. NOTCH1-p.C702fs mutation was found exclusively in the FDOVL cell line and the metastatic lymph node. The mutation promoted migration and invasion in cell and animal models, and these effects were markedly repressed by the NOTCH inhibitor LY3039478. RNA sequencing confirmed CSF3 as the downstream effector of NOTCH1 mutation. Furthermore, the mutation was significantly more common in metastatic lymph nodes than in other peritoneal metastases in 10 paired samples (60% vs. 20%). The study revealed that NOTCH1 mutation is probably a driver of lymph node metastasis in ovarian cancer, which offers new ideas for the treatment of ovarian cancer lymph node metastasis with NOTCH inhibitors.
Assuntos
Palavras-chave

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Limite: Animals / Female / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article