FES null mice demonstrate a reduction in neutrophil dependent pancreatic cancer metastatic burden
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Patients with pancreatic ductal adenocarcinoma (PDAC) have a dismal 5-year
survival rate of less than 10%, predominantly due to delayed diagnosis and a lack
of effective treatment options. In the PDAC tumor microenvironment (TME),
neutrophils are among the immune cell types that are most prevalent and are
linked to a poor clinical prognosis. However, treatments that target tumorassociated
neutrophils are limited despite recent developments in our
understanding of neutrophil function in cancer. The feline sarcoma oncogene
(FES) is a nonreceptor tyrosine kinase previously associated with leukemia and
hematopoietic homeostasis. Here we describe a newly derived FES null mouse
with no distinct phenotype and no defects in hematopoietic homeostasis
including neutrophil viability. The immune cell composition and neutrophil
population were analyzed with flow cytometry, colony-forming unit (CFU)
assay, and a neutrophil viability assay, while the response to PDAC was
examined with an in vivo cancer model. In an experimental metastasis model,
the FES null model displayed a reduced PDAC hepatic metastatic burden and a
reduction in neutrophils granulocytes. Accordingly, our results indicate FES as a
potential target for PDAC TME modulation.
survival rate of less than 10%, predominantly due to delayed diagnosis and a lack
of effective treatment options. In the PDAC tumor microenvironment (TME),
neutrophils are among the immune cell types that are most prevalent and are
linked to a poor clinical prognosis. However, treatments that target tumorassociated
neutrophils are limited despite recent developments in our
understanding of neutrophil function in cancer. The feline sarcoma oncogene
(FES) is a nonreceptor tyrosine kinase previously associated with leukemia and
hematopoietic homeostasis. Here we describe a newly derived FES null mouse
with no distinct phenotype and no defects in hematopoietic homeostasis
including neutrophil viability. The immune cell composition and neutrophil
population were analyzed with flow cytometry, colony-forming unit (CFU)
assay, and a neutrophil viability assay, while the response to PDAC was
examined with an in vivo cancer model. In an experimental metastasis model,
the FES null model displayed a reduced PDAC hepatic metastatic burden and a
reduction in neutrophils granulocytes. Accordingly, our results indicate FES as a
potential target for PDAC TME modulation.
Originalsprog | Engelsk |
---|---|
Artikelnummer | 1096499 |
Tidsskrift | Frontiers in Oncology |
Vol/bind | 13 |
Antal sider | 8 |
ISSN | 2234-943X |
DOI | |
Status | Udgivet - 2023 |
Bibliografisk note
Funding Information:
This work was supported by The European Research Council (JS, SN, and JE: ERC-2015-CoG-682881-Matrican) and The Danish Cancer Society (SN: R167-A10618). Acknowledgments
Publisher Copyright:
Copyright © 2023 Strøbech, Giuriatti, Stagaard, De Sepulveda, Nielsen and Erler.
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