Supplementary Data from Targeting the Extracellular HSP90 Co-Chaperone Morgana Inhibits Cancer Cell Migration and Promotes Anticancer Immunity

Seclì, Laura; Avalle, Lidia; Poggio, Pietro; Fragale, Giuseppe; Cannata, Cristiana; Conti, Laura; Iannucci, Andrea; Carrà, Giovanna; Rubinetto, Cristina; Miniscalco, Barbara; Hirsch, Emilio; Poli, Valeria; Morotti, Alessandro; De Andrea, Marco; Turco, Emilia; Cavallo, Federica; Fusella, Federica; Brancaccio, Mara

doi:10.1158/0008-5472.22428814.v1

00085472can203150-sup-251664_2_supp_7208403_qv5zl7.pdf (320.65 kB)

Supplementary Data from Targeting the Extracellular HSP90 Co-Chaperone Morgana Inhibits Cancer Cell Migration and Promotes Anticancer Immunity

journal contribution

posted on 2023-03-31, 04:25 authored by Laura Seclì, Lidia Avalle, Pietro Poggio, Giuseppe Fragale, Cristiana Cannata, Laura Conti, Andrea Iannucci, Giovanna Carrà, Cristina Rubinetto, Barbara Miniscalco, Emilio Hirsch, Valeria Poli, Alessandro Morotti, Marco De Andrea, Emilia Turco, Federica Cavallo, Federica Fusella, Mara Brancaccio

Supplementary Materials

Funding

AIRC

History

ARTICLE ABSTRACT

HSP90 is secreted by cancer cells into the extracellular milieu, where it exerts protumoral activities by activating extracellular substrate proteins and triggering autocrine signals through cancer cell surface receptors. Emerging evidence indicates that HSP90 co-chaperones are also secreted and may direct HSP90 extracellular activities. In this study, we found that the HSP90 co-chaperone Morgana is released by cancer cells and, in association with HSP90, induces cancer cell migration through TLR2, TLR4, and LRP1. In syngeneic cancer mouse models, a mAb targeting Morgana extracellular activity reduced primary tumor growth via macrophage-dependent recruitment of CD8+ T lymphocytes, blocked cancer cell migration, and inhibited metastatic spreading. Overall, these data define Morgana as a new player in the HSP90 extracellular interactome and suggest that Morgana may regulate HSP90 activity to promote cancer cell migration and suppress antitumor immunity. This work suggests the potential therapeutic value of targeting the extracellular HSP90 co-chaperone Morgana to inhibit metastasis formation and enhance the CD8+ T-cell–mediated antitumor immune response.