PMID- 19155309
OWN - NLM
STAT- MEDLINE
DCOM- 20090323
LR  - 20220419
IS  - 1538-7445 (Electronic)
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 69
IP  - 3
DP  - 2009 Feb 1
TI  - Beta1 integrin adhesion enhances IL-6-mediated STAT3 signaling in myeloma cells: 
      implications for microenvironment influence on tumor survival and proliferation.
PG  - 1009-15
LID - 10.1158/0008-5472.CAN-08-2419 [doi]
AB  - The bone marrow microenvironmental components interleukin (IL)-6 and fibronectin 
      (FN) individually influence the proliferation and survival of multiple myeloma 
      (MM) cells; however, in vivo, these effectors most likely work together. We 
      examined signaling events, cell cycle progression, and levels of drug response in 
      MM cells either adhered to FN via beta1 integrins, stimulated with IL-6, or 
      treated with the two combined. Although G(1)-S cell cycle arrest associated with 
      FN adhesion was overcome when IL-6 was added, the cell adhesion-mediated drug 
      resistance (CAM-DR) was maintained in the presence of IL-6. Concomitant exposure 
      of MM cells to IL-6 and FN adhesion revealed a dramatic increase in signal 
      transducers and activators of transcription 3 (STAT3) phosphorylation, nuclear 
      translocation, and DNA binding, compared with either IL-6 or FN adhesion alone in 
      four MM cell lines. Importantly, this increase in STAT3 activation correlated 
      with a novel association between STAT3 and gp130 in cells adhered to FN before 
      stimulation with IL-6, relative to nonadherent cells. Taken together, these 
      results suggest a mechanism by which collaborative signaling by beta1 integrin 
      and gp130 confers an increased survival advantage to MM cells.
FAU - Shain, Kenneth H
AU  - Shain KH
AD  - Experimental Therapeutics and Oncologic Sciences Program, H Lee Moffitt Cancer 
      Center and Research Institute, Tampa, Florida 33612, USA.
FAU - Yarde, Danielle N
AU  - Yarde DN
FAU - Meads, Mark B
AU  - Meads MB
FAU - Huang, Mei
AU  - Huang M
FAU - Jove, Richard
AU  - Jove R
FAU - Hazlehurst, Lori A
AU  - Hazlehurst LA
FAU - Dalton, William S
AU  - Dalton WS
LA  - eng
GR  - R01 CA077859/CA/NCI NIH HHS/United States
GR  - 77859/PHS HHS/United States
GR  - R01 CA077859-10/CA/NCI NIH HHS/United States
GR  - P30 CA076292/CA/NCI NIH HHS/United States
GR  - CA-82533/CA/NCI NIH HHS/United States
GR  - P01 CA082533/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20090120
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (DNA, Neoplasm)
RN  - 0 (Fibronectins)
RN  - 0 (Integrin beta1)
RN  - 0 (Interleukin-6)
RN  - 0 (STAT3 Transcription Factor)
RN  - 0 (STAT3 protein, human)
RN  - 133483-10-0 (Cytokine Receptor gp130)
SB  - IM
MH  - Cell Adhesion/physiology
MH  - Cell Growth Processes/physiology
MH  - Cell Line, Tumor
MH  - Cytokine Receptor gp130/metabolism
MH  - DNA, Neoplasm/metabolism
MH  - Drug Resistance, Neoplasm
MH  - Fibronectins/metabolism
MH  - Humans
MH  - Integrin beta1/*metabolism
MH  - Interleukin-6/*metabolism/pharmacology
MH  - Multiple Myeloma/metabolism/*pathology
MH  - Phosphorylation
MH  - STAT3 Transcription Factor/*metabolism
MH  - Signal Transduction
PMC - PMC2680075
MID - NIHMS92514
EDAT- 2009/01/22 09:00
MHDA- 2009/03/24 09:00
PMCR- 2010/02/01
CRDT- 2009/01/22 09:00
PHST- 2009/01/22 09:00 [entrez]
PHST- 2009/01/22 09:00 [pubmed]
PHST- 2009/03/24 09:00 [medline]
PHST- 2010/02/01 00:00 [pmc-release]
AID - 0008-5472.CAN-08-2419 [pii]
AID - 10.1158/0008-5472.CAN-08-2419 [doi]
PST - ppublish
SO  - Cancer Res. 2009 Feb 1;69(3):1009-15. doi: 10.1158/0008-5472.CAN-08-2419. Epub 
      2009 Jan 20.