PMID- 18469856
OWN - NLM
STAT- MEDLINE
DCOM- 20080930
LR  - 20080904
IS  - 1476-5594 (Electronic)
IS  - 0950-9232 (Linking)
VI  - 27
IP  - 39
DP  - 2008 Sep 4
TI  - Identification of a novel switch in the dominant forms of cell adhesion-mediated 
      drug resistance in glioblastoma cells.
PG  - 5169-81
LID - 10.1038/onc.2008.148 [doi]
AB  - The failure of malignant cells to undergo apoptosis is a major obstacle in cancer 
      therapy, and thus identifying the underlining molecules involved therein is 
      imperative for improving patient survival. An important mechanism of drug 
      resistance is cell adhesion-mediated drug resistance (CAM-DR). In this study we 
      identify a novel switch by which glioblastoma multiforme (GBM) cells alter the 
      mode of CAM-DR. In the absence of a microenvironmental cue provided by components 
      of the extracellular matrix (ECM), GBM cells are able to employ an alternative, 
      but equally effective, mode of CAM-DR by forming spheres via cell-cell 
      interactions. Intriguingly, when inhibiting cell-cell interactions in the absence 
      of ECM components, either by low cell density or by inhibition of gap junctions 
      (intercellular connexin tunnels) through chemical inhibition with carbenoxyolone 
      or co-incubation with the connexin-mimicking Gap 27 Cx37,43 peptide, GBM cells 
      were sensitized to tumor necrosis factor-related apoptosis-inducing ligand- and 
      CD95-induced apoptosis. By demonstrating that GBM cells can alternate from one 
      form of CAM-DR (cell-substrate tethering) to another (homocellular cell-cell 
      adhesion) and that inhibition of both forms is necessary for apoptosis 
      sensitization, our findings not only have important implications for novel 
      approaches to restore defective apoptosis programs, but also reveal a novel role 
      of gap junctions in GBM.
FAU - Westhoff, M A
AU  - Westhoff MA
AD  - Department of Hematology/Oncology, University Children's Hospital, Ulm, Germany.
FAU - Zhou, S
AU  - Zhou S
FAU - Bachem, M G
AU  - Bachem MG
FAU - Debatin, K M
AU  - Debatin KM
FAU - Fulda, S
AU  - Fulda S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20080512
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Extracellular Matrix Proteins)
SB  - IM
MH  - Antineoplastic Agents/pharmacology
MH  - Apoptosis/drug effects
MH  - Brain Neoplasms/genetics/metabolism/*pathology
MH  - Cell Adhesion/*genetics
MH  - Cell Cycle
MH  - Cell Line, Tumor
MH  - *Drug Resistance, Neoplasm
MH  - Extracellular Matrix Proteins/metabolism
MH  - Glioblastoma/genetics/metabolism/*pathology
MH  - Humans
MH  - Signal Transduction
EDAT- 2008/05/13 09:00
MHDA- 2008/10/01 09:00
CRDT- 2008/05/13 09:00
PHST- 2008/05/13 09:00 [pubmed]
PHST- 2008/10/01 09:00 [medline]
PHST- 2008/05/13 09:00 [entrez]
AID - onc2008148 [pii]
AID - 10.1038/onc.2008.148 [doi]
PST - ppublish
SO  - Oncogene. 2008 Sep 4;27(39):5169-81. doi: 10.1038/onc.2008.148. Epub 2008 May 12.