PMID- 17684491
OWN - NLM
STAT- MEDLINE
DCOM- 20080304
LR  - 20220309
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 7
DP  - 2008 Feb 7
TI  - Microglia-derived TGF-beta as an important regulator of glioblastoma invasion--an 
      inhibition of TGF-beta-dependent effects by shRNA against human TGF-beta type II 
      receptor.
PG  - 918-30
AB  - The invasion of tumor cells into brain tissue is a pathologic hallmark of 
      malignant gliomas and contributes to treatment failures. Diffuse glioblastomas 
      contain numerous microglial cells, which enhance the progression of gliomas; 
      however, factors responsible for invasion-promoting role of microglia are 
      unknown. Transforming growth factor-beta (TGF-beta) can enhance tumor growth, 
      invasion, angiogenesis and immunosuppression. Antagonizing TGF-beta activity has 
      been shown to inhibit tumor invasion in vitro and tumorigenicity, but a systemic 
      inhibition or lack of TGF-beta signaling results in acute inflammation and 
      disruption of immune system homeostasis. We developed plasmid-transcribed small 
      hairpin RNAs (shRNAs) to downregulate the TGF-beta type II receptor (TbetaIIR) 
      expression, which effectively inhibited cytokine-induced signaling pathways and 
      transcriptional responses in transiently transfected human glioblastoma cells. 
      Silencing of TbetaIIR abolished TGF-beta-induced glioblastoma invasiveness and 
      migratory responses in vitro. Moreover, tumorigenicity of glioblastoma cells 
      stably expressing TbetaIIR shRNAs in nude mice was reduced by 50%. Microglia 
      strongly enhanced glioma invasiveness in the co-culture system, but this 
      invasion-promoting activity was lost in glioma cells stably expressing 
      shTbetaRII, indicating a crucial role of microglia-derived TGF-beta in tumor-host 
      interactions. Our results demonstrate a successful targeting of 
      TGF-beta-dependent invasiveness and tumorigenicity of glioblastoma cells by 
      RNAi-mediated gene silencing.
FAU - Wesolowska, A
AU  - Wesolowska A
AD  - Laboratory of Transcription Regulation, Department of Cell Biology, Nencki 
      Institute of Experimental Biology, Warsaw, Poland.
FAU - Kwiatkowska, A
AU  - Kwiatkowska A
FAU - Slomnicki, L
AU  - Slomnicki L
FAU - Dembinski, M
AU  - Dembinski M
FAU - Master, A
AU  - Master A
FAU - Sliwa, M
AU  - Sliwa M
FAU - Franciszkiewicz, K
AU  - Franciszkiewicz K
FAU - Chouaib, S
AU  - Chouaib S
FAU - Kaminska, B
AU  - Kaminska B
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070806
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Drug Combinations)
RN  - 0 (Laminin)
RN  - 0 (Proteoglycans)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, Transforming Growth Factor beta)
RN  - 0 (Transforming Growth Factor beta)
RN  - 119978-18-6 (matrigel)
RN  - 9007-34-5 (Collagen)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.30 (Receptor, Transforming Growth Factor-beta Type II)
SB  - IM
MH  - Animals
MH  - Cell Movement/*physiology
MH  - Coculture Techniques
MH  - Collagen/metabolism
MH  - Drug Combinations
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Flow Cytometry
MH  - Gene Silencing/*physiology
MH  - Glioma/metabolism/*pathology
MH  - Humans
MH  - Laminin/metabolism
MH  - Male
MH  - Mice
MH  - Mice, Nude
MH  - Microglia/*metabolism
MH  - Neoplasm Invasiveness
MH  - Protein Serine-Threonine Kinases/*genetics/metabolism
MH  - Proteoglycans/metabolism
MH  - RNA, Messenger/metabolism
MH  - Rats
MH  - Receptor, Transforming Growth Factor-beta Type II
MH  - Receptors, Transforming Growth Factor beta/*genetics/metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Signal Transduction
MH  - Transfection
MH  - Transforming Growth Factor beta/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2007/08/09 09:00
MHDA- 2008/03/05 09:00
CRDT- 2007/08/09 09:00
PHST- 2007/08/09 09:00 [pubmed]
PHST- 2008/03/05 09:00 [medline]
PHST- 2007/08/09 09:00 [entrez]
AID - 1210683 [pii]
AID - 10.1038/sj.onc.1210683 [doi]
PST - ppublish
SO  - Oncogene. 2008 Feb 7;27(7):918-30. doi: 10.1038/sj.onc.1210683. Epub 2007 Aug 6.