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

Abstract

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 β1 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.

• Authors: Masato Yoshihara, Yoshihiko Yamakita, Hiroaki Kajiyama, Takeshi Senga, Yoshihiro Koya, Mamoru Yamashita, Akihiro Nawa, Fumitaka Kikkawa
• Journal: Experimental cell research (Exp Cell Res) Vol. 392 Issue 2 Pg. 112011 (07 15 2020) ISSN: 1090-2422 [Electronic] United States
• PMID: 32339607 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers, Tumor
• Carrier Proteins
• FSCN1 protein, human
• Integrin beta1
• MYO10 protein, human
• Microfilament Proteins
• Myosins

Topics

• Biomarkers, Tumor (genetics, metabolism)
• Carrier Proteins (genetics, metabolism)
• Cell Adhesion
• Cell Movement
• Epithelium (metabolism, pathology)
• Female
• Humans
• Integrin beta1 (genetics, metabolism)
• Microfilament Proteins (genetics, metabolism)
• Myosins (genetics, metabolism)
• Ovarian Neoplasms (genetics, metabolism, pathology)
• Peritoneal Neoplasms (genetics, metabolism, secondary)
• Prognosis
• Pseudopodia (genetics, metabolism, pathology)
• Survival Rate
• Tumor Cells, Cultured