Involvement of small extracellular vesicle-derived TIE-1 in the chemoresistance of ovarian cancer cells

Tomoka Misawa, Masafumi Toyoshima, Kazuyuki Kitatani, Masumi Ishibashi, Junko Hasegawa-Minato, Shogo Shigeta, Nobuo Yaegashi

Research output: Contribution to journalArticlepeer-review

1 Citation (Scopus)


Background: Ovarian cancer is the most lethal gynecologic malignancy due to the tumor's acquisition of chemoresistance to platinum-based chemotherapy. To solve this problem, we conducted RNAi-based large-scale screening and determined that tyrosine kinase with immunoglobulin-like and EGF-like domains 1 (TIE-1) is a key molecule involved in the platinum resistance of ovarian cancer cells. Recently, a variety of studies have investigated that small extracellular vesicles (sEVs) contribute to the communication between cancer cells, including the development of chemoresistance in ovarian cancer. The purpose of our study is to determine if sEVs-derived TIE-1 is involved in the chemoresistance of ovarian cancer cells. Materials and Methods: TIE-1-overexpressed TOV112D cells, termed TOV112DTIE-1 cells, were established, and sEVs were isolated from TOV112DTIE-1 cells supernatants by ultracentrifugation. We assessed cisplatin sensitivity in recipient cells with TOV112DTIE-1-derived sEVs by cell-Titer Glo kit. We also asked whether sEV-derived TIE-1 suppressed the DNA damage response in recipient cells and evaluated the DNA damage response by counting cells positive for DNA damage foci. Results: TIE-1 was contained within sEVTIE-1 derived from the cellular supernatant of TOV112DTIE-1. We showed that sEV-derived TIE-1 decreased chemosensitivity to cisplatin by suppressing the DNA damage response in recipient cells. Conclusion: Our findings suggest that sEV-derived TIE-1 could be a new therapeutic target for refractory ovarian cancer.

Original languageEnglish
Article number100364
JournalCancer Treatment and Research Communications
Publication statusPublished - 2021 Jan


  • Chemoresistance
  • Cisplatin
  • Ovarian cancer
  • Small extracellular vesicles
  • TIE-1

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Involvement of small extracellular vesicle-derived TIE-1 in the chemoresistance of ovarian cancer cells'. Together they form a unique fingerprint.

Cite this