PMID- 34465584
OWN - NLM
STAT- MEDLINE
DCOM- 20220325
LR  - 20220325
IS  - 1557-3125 (Electronic)
IS  - 1541-7786 (Linking)
VI  - 19
IP  - 12
DP  - 2021 Dec
TI  - Opposing Effects of Granulocyte Colony-Stimulating Factor on the Initiation and 
      Progression of Breast Cancer Bone Metastases.
PG  - 2110-2119
LID - 10.1158/1541-7786.MCR-21-0243 [doi]
AB  - 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.
CI  - (c)2021 American Association for Cancer Research.
FAU - Hiraga, Toru
AU  - Hiraga T
AUID- ORCID: 0000-0002-7829-2395
AD  - Department of Histology and Cell Biology, Matsumoto Dental University, 
      Shiojiri-shi, Nagano, Japan. toru.hiraga@mdu.ac.jp.
FAU - Ito, Susumu
AU  - Ito S
AD  - Division of Instrumental Analysis, Research Center for Human and Environmental 
      Sciences, Shinshu University, Matsumoto-shi, Nagano, Japan.
FAU - Mizoguchi, Toshihide
AU  - Mizoguchi T
AUID- ORCID: 0000-0001-9910-6419
AD  - Institute for Oral Science, Matsumoto Dental University, Shiojiri-shi, Nagano, 
      Japan.
AD  - Oral Health Science Center, Tokyo Dental College, Chiyoda-ku, Tokyo, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20210831
PL  - United States
TA  - Mol Cancer Res
JT  - Molecular cancer research : MCR
JID - 101150042
RN  - 143011-72-7 (Granulocyte Colony-Stimulating Factor)
SB  - IM
MH  - Animals
MH  - Bone Neoplasms/pathology/*secondary
MH  - Breast Neoplasms/*complications/*genetics
MH  - Cell Line, Tumor
MH  - Disease Progression
MH  - Female
MH  - Granulocyte Colony-Stimulating Factor/*metabolism
MH  - Humans
MH  - Mice
MH  - Neoplasm Metastasis
EDAT- 2021/09/02 06:00
MHDA- 2022/03/26 06:00
CRDT- 2021/09/01 06:40
PHST- 2021/04/02 00:00 [received]
PHST- 2021/07/09 00:00 [revised]
PHST- 2021/08/27 00:00 [accepted]
PHST- 2021/09/02 06:00 [pubmed]
PHST- 2022/03/26 06:00 [medline]
PHST- 2021/09/01 06:40 [entrez]
AID - 1541-7786.MCR-21-0243 [pii]
AID - 10.1158/1541-7786.MCR-21-0243 [doi]
PST - ppublish
SO  - Mol Cancer Res. 2021 Dec;19(12):2110-2119. doi: 10.1158/1541-7786.MCR-21-0243. 
      Epub 2021 Aug 31.