Retraction fibers produced by fibronectin-integrin α5β1 interaction promote motility of brain tumor cells

Seon Yong Lee, Sang Hun Choi, Min Seok Lee, Amanzhol Kurmashev, Hae Nim Lee, Young Gyu Ko, Kanghun Lee, Sohee Jeong, Jihye Seong, Joo H. Kang, Hyunggee Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Glioblastoma (GBM) is a refractory disease that has a highly infiltrative characteristic. Over the past decade, GBM perivascular niche (PVN) has been described as a route of dissemination. Here, we investigated that trailed membrane structures, namely retraction fibers (RFs), are formed by perivascular extracellular matrix (ECM) proteins. By using the anatomical GBM database, we validated that the ECM-related genes were highly expressed in the cells within the PVN where fibronectin (FN) induced RF formation. By disrupting candidates of FN-binding integrins, integrin α5β1 was identified as the main regulator of RF formation. De novo RFs were produced at the trailing edge, and focal adhesions were actively localized in RFs, indicating that adhesive force makes RFs remain at the bottom surface. Furthermore, we observed that GBM cells more frequently migrated along the residual RFs formed by preceding cells in microfluidic channels in comparison to those in the channels without RFs, suggesting that the infiltrative characteristics GBM could be attributed to RFs formed by the preceding cells in concert with chemoattractant cues. Altogether, we demonstrated that shedding membrane structures of GBM cells are maintained by FN-integrin α5β1 interaction and promoted their motility.

Original languageEnglish
Article numbere21906
JournalFASEB Journal
Volume35
Issue number10
DOIs
Publication statusPublished - 2021 Oct

Keywords

  • cell migration
  • fibronectin
  • integrin α5β1
  • perivascular niche
  • retraction fiber

ASJC Scopus subject areas

  • Biotechnology
  • Biochemistry
  • Molecular Biology
  • Genetics

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