HSPs/STAT3 Interplay Sustains DDR and Promotes Cytokine Release by Primary Effusion Lymphoma Cells

Int J Mol Sci. 2023 Feb 15;24(4):3933. doi: 10.3390/ijms24043933.

Abstract

Primary effusion lymphoma (PEL) is a rare and aggressive B-cell lymphoma, against which current therapies usually fail. In the present study, we show that targeting HSPs, such as HSP27, HSP70 and HSP90, could be an efficient strategy to reduce PEL cell survival, as it induces strong DNA damage, which correlated with an impairment of DDR. Moreover, as HSP27, HSP70 and HSP90 cross talk with STAT3, their inhibition results in STAT3 de-phosphorylation and. On the other hand, the inhibition of STAT3 may downregulate these HSPs. These findings suggest that targeting HSPs has important implications in cancer therapy, as it can reduce the release of cytokines by PEL cells, which, besides affecting their own survival, could negatively influence anti-cancer immune response.

Keywords: DDR; HSP27; HSP70; HSP90; PEL; STAT3; cytokines.

MeSH terms

  • Apoptosis
  • Cell Line, Tumor
  • Cytokines
  • DNA Damage*
  • HSP27 Heat-Shock Proteins* / metabolism
  • HSP70 Heat-Shock Proteins* / metabolism
  • HSP90 Heat-Shock Proteins* / metabolism
  • Humans
  • Lymphoma, Primary Effusion* / drug therapy
  • Lymphoma, Primary Effusion* / genetics
  • Molecular Targeted Therapy*
  • STAT3 Transcription Factor / metabolism

Substances

  • Cytokines
  • HSP27 Heat-Shock Proteins
  • HSP70 Heat-Shock Proteins
  • HSP90 Heat-Shock Proteins
  • STAT3 protein, human
  • STAT3 Transcription Factor