Osteopontin is a therapeutic target that drives breast cancer recurrence.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
24 Oct 2024
24 Oct 2024
Historique:
received:
05
04
2024
accepted:
29
09
2024
medline:
25
10
2024
pubmed:
25
10
2024
entrez:
25
10
2024
Statut:
epublish
Résumé
Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin's multiaxial role in breast cancer progression and recurrence.
Identifiants
pubmed: 39448577
doi: 10.1038/s41467-024-53023-9
pii: 10.1038/s41467-024-53023-9
doi:
Substances chimiques
Osteopontin
106441-73-0
SPP1 protein, human
0
Interleukin-4
207137-56-2
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
9174Subventions
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : FDN-148373
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : PLL - 190347
Organisme : Gouvernement du Canada | Canadian Institutes of Health Research (Instituts de Recherche en Santé du Canada)
ID : 187660
Organisme : Canadian Cancer Society Research Institute (Société Canadienne du Cancer)
ID : 706679
Organisme : Canadian Cancer Society Research Institute (Société Canadienne du Cancer)
ID : 706216
Organisme : Canadian Cancer Society Research Institute (Société Canadienne du Cancer)
ID : 708195
Informations de copyright
© 2024. The Author(s).
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