IGFBP-2 acts as a tumour suppressor and plays a role in determining chemosensitivity in bladder cancer cells

Zhen Tang, David Gillatt, Anthony Koupparis, Jeff M. P. Holly, Claire M Perks

Research output: Contribution to journalArticle (Academic Journal)peer-review

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Abstract

There are mixed reports on the role that IGFBP-2 plays in cancer progression, with some indicating a tumour suppressive role and others showing that IGFBP-2 may act as an oncogene. These apparent contradictions may be context and tissue specific. In this study we determined the role that IGFBP-2 played on the phenotype and chemosensitivity of a selection of bladder cancer cell lines and investigated how the abundance of IGFBP-2 was regulated. We found that IGFBP-2 was more abundant in the epithelial bladder cancer cells, RT4 and UMUC3 and absent in the more mesenchymal T24 and TCCSUP cells. Silencing IGFBP-2 using siRNA in epithelial RT4 cells promoted cell proliferation, invasion, colony formation, resulted in a reduction in epithelial (E-cadherin) and an increase in mesenchymal (N-cadherin) markers and increased sensitivity to cisplatin-induced cell death. Conversely, we observed the opposite effects when adding exogenous IGFBP-2 to the mesenchymal T24 cells. We determined that IGFBP-2 was epigenetically silenced via DNA methylation as the cells adopted a mesenchymal phenotype. Collectively these data suggest that IGFBP-2 acts as a tumour suppressor and marker of chemosensitivity in epithelial bladder cancer cells and that IGFBP-2 is epigenetically silenced by methylation to promote bladder cancer progression.
Original languageEnglish
Pages (from-to)7043-7057
Number of pages15
JournalOncotarget
Volume10
Issue number66
DOIs
Publication statusPublished - 17 Dec 2019

Structured keywords

  • ICEP

Keywords

  • IGFBP-2
  • methylation
  • proliferation
  • colony formation
  • invasion
  • epithelial-to-mesenchymal transition
  • chemosensitivity

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