PMID- 24468794
OWN - NLM
STAT- MEDLINE
DCOM- 20140515
LR  - 20230216
IS  - 1530-0307 (Electronic)
IS  - 0023-6837 (Linking)
VI  - 94
IP  - 4
DP  - 2014 Apr
TI  - Colony-stimulating factor 1 potentiates lung cancer bone metastasis.
PG  - 371-81
LID - 10.1038/labinvest.2014.1 [doi]
AB  - Colony-stimulating factor 1 (CSF1) is essential for osteoclastogenesis that 
      mediates osteolysis in metastatic tumors. Patients with lung cancer have 
      increased CSF1 in serum and high levels are associated with poor survival. 
      Adenocarcinomas metastasize rapidly and many patients suffer from bone 
      metastasis. Lung cancer stem-like cells sustain tumor growth and potentiate 
      metastasis. The purpose of this study was to determine the role of CSF1 in lung 
      cancer bone metastasis and whether inhibition of CSF1 ameliorates the disease. 
      Human lung adenocarcinoma A549 cells were examined in vitro for CSF1/CSF1R. 
      A549-luc cells were injected intracardiac in NOD/SCID mice and metastasis was 
      assessed. To determine the effect of CSF1 knockdown (KD) in A549 cells on bone 
      metastasis, cells were stably transfected with a retroviral vector containing 
      short-hairpin CSF1 (KD) or empty vector (CT). Results showed that A549 cells 
      express CSF1/CSF1R; CSF1 increased their proliferation and invasion, whereas 
      soluble CSF1R inhibited invasion. Mice injected with A549-luc cells showed 
      osteolytic bone lesions 3.5 weeks after injection and lesions increased over 5 
      weeks. Tumors recapitulated adenocarcinoma morphology and showed osteoclasts 
      along the tumor/bone interface, trabecular, and cortical bone loss. Analyses of 
      KD cells showed decreased CSF1 protein levels, reduced colony formation in soft 
      agar assay, and decreased fraction of stem-like cells. In CSF1KD mice, the 
      incidence of tumor metastasis was similar to controls, although fewer CSF1KD mice 
      had metastasis in both hind limbs. KD tumors showed reduced CSF1 expression, 
      Ki-67+ cells, and osteoclasts. Importantly, there was a low incidence of large 
      tumors >0.1 mm(2) in CSF1KD mice compared with control mice (10% vs 62.5%). This 
      study established a lung osteolytic bone metastasis model that resembles human 
      disease and suggests that CSF1 is a key determinant of cancer stem cell survival 
      and tumor growth. Results may lead to novel strategies to inhibit CSF1 in lung 
      cancer and improve management of bone metastasis.
FAU - Hung, Jaclyn Y
AU  - Hung JY
AD  - Division of Hematology and Oncology, Department of Pediatrics, Greehey Children's 
      Cancer Research Institute, University of Texas Health Science Center, San 
      Antonio, TX, USA.
FAU - Horn, Diane
AU  - Horn D
AD  - Department of Pathology, University of Texas Health Science Center at San Antonio 
      and South Texas Veterans Health Care System, San Antonio, TX, USA.
FAU - Woodruff, Kathleen
AU  - Woodruff K
AD  - Department of Pathology, University of Texas Health Science Center at San Antonio 
      and South Texas Veterans Health Care System, San Antonio, TX, USA.
FAU - Prihoda, Thomas
AU  - Prihoda T
AD  - Department of Pathology, University of Texas Health Science Center at San Antonio 
      and South Texas Veterans Health Care System, San Antonio, TX, USA.
FAU - LeSaux, Claude
AU  - LeSaux C
AD  - Division of Cardiology, University of Texas Health Science Center at San Antonio, 
      San Antonio, TX, USA.
FAU - Peters, Jay
AU  - Peters J
AD  - Department of Pulmonary Medicine, University of Texas Health Science Center at 
      San Antonio and South Texas Veterans Health Care System, San Antonio, TX, USA.
FAU - Tio, Fermin
AU  - Tio F
AD  - Department of Pathology, University of Texas Health Science Center at San Antonio 
      and South Texas Veterans Health Care System, San Antonio, TX, USA.
FAU - Abboud-Werner, Sherry L
AU  - Abboud-Werner SL
AD  - Department of Pathology, University of Texas Health Science Center at San Antonio 
      and South Texas Veterans Health Care System, San Antonio, TX, USA.
LA  - eng
GR  - P30CA54174/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20140127
PL  - United States
TA  - Lab Invest
JT  - Laboratory investigation; a journal of technical methods and pathology
JID - 0376617
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor)
SB  - IM
MH  - Adenocarcinoma/metabolism/*secondary
MH  - Animals
MH  - Bone Neoplasms/metabolism/*secondary
MH  - Bone and Bones/*pathology
MH  - Cell Line, Tumor
MH  - Gene Knockdown Techniques
MH  - Humans
MH  - Lung Neoplasms/metabolism/*pathology
MH  - Macrophage Colony-Stimulating Factor/genetics/*metabolism
MH  - Mice
MH  - Mice, Inbred NOD
MH  - Mice, SCID
MH  - Neoplasm Metastasis
MH  - Neoplasms, Experimental
MH  - Neoplastic Stem Cells/physiology
MH  - Osteoclasts/physiology
MH  - Receptor, Macrophage Colony-Stimulating Factor/metabolism
EDAT- 2014/01/29 06:00
MHDA- 2014/05/16 06:00
CRDT- 2014/01/29 06:00
PHST- 2013/06/07 00:00 [received]
PHST- 2013/11/22 00:00 [revised]
PHST- 2013/12/22 00:00 [accepted]
PHST- 2014/01/29 06:00 [entrez]
PHST- 2014/01/29 06:00 [pubmed]
PHST- 2014/05/16 06:00 [medline]
AID - S0023-6837(22)00825-X [pii]
AID - 10.1038/labinvest.2014.1 [doi]
PST - ppublish
SO  - Lab Invest. 2014 Apr;94(4):371-81. doi: 10.1038/labinvest.2014.1. Epub 2014 Jan 
      27.