Osteopontin is a therapeutic target that drives breast cancer recurrence

Yu Gu, Tarek Taifour, Tung Bui, Dongmei Zuo, Alain Pacis, Alexandre Poirier, Sherif Attalla, Anne-Marie Fortier, Virginie Sanguin-Gendreau, Tien-Chi Pan, Vasilios Papavasiliou, Nancy U. Lin, Melissa E. Hughes, Kalie Smith, Morag Park, Michel L. Tremblay, Lewis A. Chodosh, Rinath Jeselsohn and William J. Muller ()
Additional contact information
Yu Gu: McGill University
Tarek Taifour: McGill University
Tung Bui: McGill University
Dongmei Zuo: McGill University
Alain Pacis: McGill University
Alexandre Poirier: McGill University
Sherif Attalla: McGill University
Anne-Marie Fortier: McGill University
Virginie Sanguin-Gendreau: McGill University
Tien-Chi Pan: University of Pennsylvania
Vasilios Papavasiliou: McGill University
Nancy U. Lin: Dana-Farber Cancer Institute
Melissa E. Hughes: Dana-Farber Cancer Institute
Kalie Smith: Dana-Farber Cancer Institute
Morag Park: McGill University
Michel L. Tremblay: McGill University
Lewis A. Chodosh: University of Pennsylvania
Rinath Jeselsohn: Dana-Farber Cancer Institute
William J. Muller: McGill University

Nature Communications, 2024, vol. 15, issue 1, 1-19

Abstract: Abstract 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.

Date: 2024
References: View references in EconPapers View complete reference list from CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-024-53023-9 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:15:y:2024:i:1:d:10.1038_s41467-024-53023-9

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-024-53023-9

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().