Opposing Effects of Granulocyte Colony-Stimulating Factor on the Initiation and Progression of Breast Cancer Bone Metastases.
Journal
Molecular cancer research : MCR
ISSN: 1557-3125
Titre abrégé: Mol Cancer Res
Pays: United States
ID NLM: 101150042
Informations de publication
Date de publication:
12 2021
12 2021
Historique:
received:
02
04
2021
revised:
09
07
2021
accepted:
27
08
2021
pubmed:
2
9
2021
medline:
26
3
2022
entrez:
1
9
2021
Statut:
ppublish
Résumé
Granulocyte colony stimulating factor (G-CSF), an essential cytokine regulating granulopoiesis, is expressed in a substantial proportion of breast cancers, and it has been implicated in cancer progression. Here, we examined effects of G-CSF on the development of bone metastases of breast cancer using immunocompetent mouse models. The expression of CXC chemokine ligand 12 (CXCL12) in bone marrow stromal cells, which plays a critical role in the maintenance of hematopoietic stem cells and also in cancer cell homing to bone, was markedly decreased in mice treated with G-CSF. Flow cytometric analysis revealed that pretreatment of mice with G-CSF reduced the number of bone-homing cancer cells. G-CSF also increased the population of myeloid-derived suppressor cells (MDSCs) in bone marrow. Depletion of MDSCs using anti-Gr-1 antibody treatment significantly decreased the metastatic tumor burden in bone. The overall effects of G-CSF on bone metastases were finally examined using two different treatment protocols. When mice were treated with G-CSF prior to the tumor cell inoculation, G-CSF did not change bone metastatic-tumor burden. In contrast, when G-CSF treatment was started after the tumor cells had homed to bone, G-CSF significantly accelerated bone metastases formation. These results suggest that G-CSF suppressed cancer cell homing to bone by downregulating CXCL12 expression in bone marrow stromal cells, whereas G-CSF stimulated the progression of bone metastases at least in part by MDSC-mediated mechanisms. IMPLICATIONS: G-CSF had opposing effects on the initiation and progression of bone metastases of breast cancer and the balance may regulate the metastatic tumor burden.
Identifiants
pubmed: 34465584
pii: 1541-7786.MCR-21-0243
doi: 10.1158/1541-7786.MCR-21-0243
doi:
Substances chimiques
Granulocyte Colony-Stimulating Factor
143011-72-7
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
2110-2119Informations de copyright
©2021 American Association for Cancer Research.
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