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Targeting the Extracellular HSP90 Co-Chaperone Morgana Inhibits Cancer Cell Migration and Promotes Anticancer

Laura Seclì1, Lidia Avalle1, Pietro Poggio1

  • 1Department of Molecular Biotechnology and Health Sciences, University of Torino, Torino, Italy.

Cancer Research
|July 1, 2021
PubMed

Insights

The HSP90 co-chaperone Morgana is secreted by cancer cells, promoting migration and metastasis. Targeting extracellular Morgana inhibits tumor growth and enhances anti-tumor immunity by recruiting CD8+ T cells.

Area of Science:

  • Oncology
  • Molecular Biology
  • Immunology

Background:

  • Heat shock protein 90 (HSP90) is secreted by cancer cells, promoting tumor growth and metastasis.
  • HSP90 co-chaperones are also secreted and may influence HSP90's extracellular functions.

Purpose of the Study:

  • To investigate the role of the HSP90 co-chaperone Morgana in cancer.
  • To determine if extracellular Morgana influences cancer cell migration and anti-tumor immunity.

Main Methods:

  • Studied Morgana secretion by cancer cells and its association with HSP90.
  • Utilized syngeneic cancer mouse models to evaluate the effects of a Morgana-targeting antibody (mAb).
  • Assessed tumor growth, cancer cell migration, metastasis, and immune cell infiltration (CD8+ T lymphocytes, macrophages).

Main Results:

  • Morgana is released by cancer cells and, with HSP90, drives cancer cell migration via TLR2, TLR4, and LRP1.
  • An anti-Morgana mAb reduced primary tumor growth by recruiting CD8+ T cells in a macrophage-dependent manner.
  • The anti-Morgana mAb inhibited cancer cell migration and metastatic spread.

Conclusions:

  • Morgana is a novel component of the extracellular HSP90 interactome, regulating HSP90 activity.
  • Extracellular Morgana promotes cancer cell migration and suppresses anti-tumor immunity.
  • Targeting extracellular Morgana represents a potential therapeutic strategy for inhibiting metastasis and enhancing CD8+ T-cell responses.

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