Filopodia play an important role in the trans-mesothelial migration of ovarian cancer cells

被引：18

作者：

Yoshihara, Masato ^{[1
,2
]}

Yamakita, Yoshihiko ^{[3
,4
]}

Kajiyama, Hiroaki ^{[1
]}

Senga, Takeshi ^{[5
]}

Koya, Yoshihiro ^{[3
,4
]}

Yamashita, Mamoru ^{[4
]}

Nawa, Akihiro ^{[3
,4
]}

Kikkawa, Fumitaka ^{[1
]}

机构：

[1] Nagoya Univ, Dept Obstet & Gynecol, Grad Sch Med, Showa Ku, Nagoya, Aichi, Japan

[2] Univ Adelaide, Adelaide Med Sch, Robinson Res Inst, Discipline Obstet & Gynaecol, Adelaide, SA, Australia

[3] Nagoya Univ, Grad Sch Med, Bell Res Ctr, Dept Obstet & Gynecol Collaborat Res,Showa Ku, Nagoya, Aichi, Japan

[4] Bell Res Ctr Reprod Hlth & Canc, Tsushima, Aichi, Japan

[5] Yahagigawa Hosp, Anjo, Aichi, Japan

来源：

EXPERIMENTAL CELL RESEARCH | 2020年 / 392卷 / 02期

基金：

日本学术振兴会;

关键词：

MYOSIN-X; UP-REGULATION; EXPRESSION; ACTIN; FASCIN; DISSEMINATION; INVADOPODIA; CORTACTIN; MOTILITY; ADHESION;

D O I：

10.1016/j.yexcr.2020.112011

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Ovarian cancer cells shed from primary tumors can spread easily to the peritoneum via the peritoneal fluid. To allow further metastasis, the cancer cells must interact with the mesothelial cell layer, which covers the entire surface of the peritoneal organs. Although the clinical importance of this interaction between cancer and mesothelial cells has been increasingly recognized, the molecular mechanisms utilized by cancer cells to adhere to and migrate through the mesothelial cell layer are poorly understood. To investigate the molecular mechanisms of cancer cell trans-mesothelial migration, we set up an in vitro trans-mesothelial migration assay using primary peritoneal mesothelial cells. Using this method, we found that downregulation of filopodial protein fascin-1 or myosin X expression in ES-2 cells significantly inhibited the rate of trans-mesothelial migration of cancer cells, whereas upregulation of fascin-1 in SK-OV-3 cells enhanced this rate. Furthermore, downregulation of N-cadherin or integrin beta 1 inhibited the rate of cancer cell trans-mesothelial migration. Conversely, downregulation of cortactin or TKS5 or treatment with the MMP inhibitor GM6001 or the N-WASP inhibitor wiskostatin did not have any effect on cancer cell trans-mesothelial migration. These results suggest that filopodia, but not lamellipodia or invadopodia, play an important role in the trans-mesothelial migration of ovarian cancer cells.

引用

页数：13