PMID- 19242604
OWN - NLM
STAT- MEDLINE
DCOM- 20090512
LR  - 20211020
IS  - 1476-5586 (Electronic)
IS  - 1522-8002 (Print)
IS  - 1476-5586 (Linking)
VI  - 11
IP  - 3
DP  - 2009 Mar
TI  - Monocyte chemotactic protein 1 promotes lung cancer-induced bone resorptive 
      lesions in vivo.
PG  - 228-36
AB  - Lung cancer is the leading cause of cancer-related deaths. The morbidity and 
      mortality of lung cancer have markedly increased in the past decade with at least 
      75% of patients with lung cancer having evidence of metastases at the time of 
      diagnosis. It frequently metastasizes to bone resulting in osteolytic lesions 
      with unknown mechanisms. The aim of this study was to identify factors that 
      mediate lung cancer-induced osteoclast activity in vivo. Using a human cytokine 
      antibody array, we first determined cytokine levels in a conditioned medium 
      collected from non-small cell lung cancer A549 and H1299 cells and the 
      non-neoplastic human bronchial epithelial BEAS2B cells. Both A549 and H1229 cells 
      produced significantly higher amount of several cytokines including monocyte 
      chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) compared with BEAS2B 
      cells. These findings were confirmed by ELISA. From clinical serum specimens, we 
      also observed that MCP-1 and IL-8 levels were increased in lung cancer patients 
      with bone metastases compared with the patients with localized tumor. Next, we 
      investigated the effects of MCP-1 on osteoclast formation in vitro using murine 
      bone marrow-derived monocytes. A549 conditioned medium induced osteoclast 
      formation that was inhibited by neutralizing antibodies against MCP-1. Finally, 
      A549 cells were stably transfected with MCP-1 short hairpin RNA. The MCP-1 
      knockdown A549 cells were implanted into the tibia of severe combined 
      immunodeficient mice for 4 weeks. The MCP-1 knockdown significantly diminished 
      A549 cell growth. We conclude that MCP-1 promotes lung cancer-induced osteoclast 
      activity and thus bone resorptive lesions in vivo.
FAU - Cai, Zhong
AU  - Cai Z
AD  - Department of Medicine, Division of Hematology & Oncology, University of 
      Pittsburgh, Pittsburgh, PA 15240, USA.
FAU - Chen, Qiuyan
AU  - Chen Q
FAU - Chen, Jun
AU  - Chen J
FAU - Lu, Yi
AU  - Lu Y
FAU - Xiao, Guozhi
AU  - Xiao G
FAU - Wu, Zhihao
AU  - Wu Z
FAU - Zhou, Qinghua
AU  - Zhou Q
FAU - Zhang, Jian
AU  - Zhang J
LA  - eng
GR  - R01 AR059647/AR/NIAMS NIH HHS/United States
GR  - R01 DK072230/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PL  - United States
TA  - Neoplasia
JT  - Neoplasia (New York, N.Y.)
JID - 100886622
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Interleukin-8)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Animals
MH  - Bone Neoplasms/*metabolism/*secondary
MH  - Carcinoma, Non-Small-Cell Lung/metabolism/*secondary
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*biosynthesis/blood
MH  - Culture Media, Conditioned/chemistry/metabolism
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Humans
MH  - Interleukin-8/biosynthesis/blood
MH  - Lung Neoplasms/*metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, SCID
MH  - Middle Aged
MH  - Osteoclasts/metabolism
PMC - PMC2647725
EDAT- 2009/02/27 09:00
MHDA- 2009/05/13 09:00
CRDT- 2009/02/27 09:00
PHST- 2008/10/05 00:00 [received]
PHST- 2008/12/03 00:00 [revised]
PHST- 2008/12/08 00:00 [accepted]
PHST- 2009/02/27 09:00 [entrez]
PHST- 2009/02/27 09:00 [pubmed]
PHST- 2009/05/13 09:00 [medline]
AID - 81282 [pii]
AID - 10.1593/neo.81282 [doi]
PST - ppublish
SO  - Neoplasia. 2009 Mar;11(3):228-36. doi: 10.1593/neo.81282.