PMID- 23917077
OWN - NLM
STAT- MEDLINE
DCOM- 20140403
LR  - 20201218
IS  - 1460-2180 (Electronic)
IS  - 0143-3334 (Linking)
VI  - 35
IP  - 1
DP  - 2014 Jan
TI  - Cancer-promoting role of adipocytes in asbestos-induced mesothelial 
      carcinogenesis through dysregulated adipocytokine production.
PG  - 164-72
LID - 10.1093/carcin/bgt267 [doi]
AB  - Like many other human cancers, the development of malignant mesothelioma is 
      closely associated with a chronic inflammatory condition. Both macrophages and 
      mesothelial cells play crucial roles in the inflammatory response caused by 
      asbestos exposure. Here, we show that adipocytes can also contribute to 
      asbestos-induced inflammation through dysregulated adipocytokine production. 
      3T3-L1 preadipocytes were differentiated into mature adipocytes prior to use. 
      These cells took up asbestos fibers (chrysotile, crocidolite and amosite) but 
      were more resistant to asbestos-induced injury than macrophages and mesothelial 
      cells. Expression microarray analysis followed by reverse transcription-PCR 
      revealed that adipocytes respond directly to asbestos exposure with an increased 
      production of proinflammatory adipocytokines [e.g. monocyte chemoattractant 
      protein-1 (MCP-1)], whereas the production of anti-inflammatory adipocytokines 
      (e.g. adiponectin) is suppressed. This was confirmed in epididymal fat pad of 
      mice after intraperitoneal injection of asbestos fibers. Such dysregulated 
      adipocytokine production favors the establishment of a proinflammatory 
      environment. Furthermore, MCP-1 marginally promoted the growth of MeT-5A 
      mesothelial cells and significantly enhanced the wound healing of Y-MESO-8A and 
      Y-MESO-8D human mesothelioma cells. Our results suggest that increased levels of 
      adipocytokines, such as MCP-1, can potentially contribute to the promotion of 
      mesothelial carcinogenesis through the enhanced recruitment of inflammatory cells 
      as well as a direct growth and migration stimulatory effect on mesothelial and 
      mesothelioma cells. Taken together, our findings support a potential 
      cancer-promoting role of adipocytes in asbestos-induced mesothelial 
      carcinogenesis.
FAU - Chew, Shan Hwu
AU  - Chew SH
AD  - Department of Pathology and Biological Responses, Nagoya University Graduate 
      School of Medicine, Nagoya 466-8550, Japan.
FAU - Okazaki, Yasumasa
AU  - Okazaki Y
FAU - Nagai, Hirotaka
AU  - Nagai H
FAU - Misawa, Nobuaki
AU  - Misawa N
FAU - Akatsuka, Shinya
AU  - Akatsuka S
FAU - Yamashita, Kyoko
AU  - Yamashita K
FAU - Jiang, Li
AU  - Jiang L
FAU - Yamashita, Yoriko
AU  - Yamashita Y
FAU - Noguchi, Michio
AU  - Noguchi M
FAU - Hosoda, Kiminori
AU  - Hosoda K
FAU - Sekido, Yoshitaka
AU  - Sekido Y
FAU - Takahashi, Takashi
AU  - Takahashi T
FAU - Toyokuni, Shinya
AU  - Toyokuni S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130805
PL  - England
TA  - Carcinogenesis
JT  - Carcinogenesis
JID - 8008055
RN  - 0 (Adipokines)
RN  - 0 (Ccl2 protein, mouse)
RN  - 0 (Chemokine CCL2)
RN  - 1332-21-4 (Asbestos)
SB  - IM
MH  - 3T3-L1 Cells
MH  - Adipocytes/metabolism/*pathology
MH  - Adipokines/metabolism
MH  - Adipose Tissue/drug effects/metabolism
MH  - Animals
MH  - Asbestos/pharmacokinetics/*toxicity
MH  - Chemokine CCL2/genetics/metabolism
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Lung Neoplasms/*chemically induced/*pathology
MH  - Male
MH  - Mesothelioma/*chemically induced/*pathology
MH  - Mesothelioma, Malignant
MH  - Mice
MH  - Mice, Inbred Strains
EDAT- 2013/08/07 06:00
MHDA- 2014/04/04 06:00
CRDT- 2013/08/07 06:00
PHST- 2013/08/07 06:00 [entrez]
PHST- 2013/08/07 06:00 [pubmed]
PHST- 2014/04/04 06:00 [medline]
AID - bgt267 [pii]
AID - 10.1093/carcin/bgt267 [doi]
PST - ppublish
SO  - Carcinogenesis. 2014 Jan;35(1):164-72. doi: 10.1093/carcin/bgt267. Epub 2013 Aug 
      5.