PMID- 18172271
OWN - NLM
STAT- MEDLINE
DCOM- 20080327
LR  - 20231213
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 14
IP  - 1
DP  - 2008 Jan 1
TI  - Interleukin-13 receptor alpha 2, EphA2, and Fos-related antigen 1 as molecular 
      denominators of high-grade astrocytomas and specific targets for combinatorial 
      therapy.
PG  - 199-208
LID - 10.1158/1078-0432.CCR-07-1990 [doi]
AB  - PURPOSE: We investigated the expression of interleukin-13 receptor alpha2 (IL-13R 
      alpha 2), EphA2, and Fos-related antigen 1 (Fra-1) in astrocytomas and normal 
      brain. We sought to document whether the expression of the three factors changed 
      with progression to higher grade malignancy and whether two or three targets in 
      combination might be sufficient to target all patients with high-grade 
      astrocytomas. EXPERIMENTAL DESIGN: Immunohistochemistry was done for IL-13R alpha 
      2, EphA2, and Fra-1 using human brain tumor tissue microarrays containing 30 
      specimens of WHO grades II and III astrocytomas, 46 glioblastoma multiformes 
      (GBM), and 9 normal brain samples. Sections were scored based on frequency and 
      intensity of expression. Western blotting was done for all three markers using 
      GBM tumor specimens and xenograft cell lines. Two cytotoxins, IL-13.E13K.PE38QQR 
      and ephrinA1-PE38QQR, which target IL-13R alpha 2 or EphA2, respectively, were 
      tested for cytotoxicity against human GBM primary explant cells and established 
      cells. RESULTS: Expression of all three proteins was significantly higher in GBM 
      compared with normal brain, low-grade, and anaplastic astrocytomas. Greater than 
      95% of GBM overexpressed at least two of the three markers. Importantly, every 
      GBM overexpressed at least one marker. Human GBM primary explant cells and cell 
      lines were potently killed by IL-13.E13K.PE38QQR and ephrinA1-PE38QQR, in 
      accordance with their level of expression of IL-13R alpha 2 and EphA2, 
      respectively. CONCLUSIONS: IL-13R alpha 2, EphA2, and Fra-1 are attractive 
      therapeutic targets representing molecular denominators of high-grade 
      astrocytomas. One hundred percent of GBM tumors overexpress at least one of these 
      proteins, providing the basis for rational combinatorial targeted 
      therapies/diagnostics suitable for all patients with this disease.
FAU - Wykosky, Jill
AU  - Wykosky J
AD  - Brain Tumor Center of Excellence, Comprehensive Cancer Center, Department of 
      Neurosurgery, Wake Forest University School of Medicine, Winston-Salem, North 
      Carolina 27157, USA.
FAU - Gibo, Denise M
AU  - Gibo DM
FAU - Stanton, Constance
AU  - Stanton C
FAU - Debinski, Waldemar
AU  - Debinski W
LA  - eng
GR  - 1F31 NS055533-01/NS/NINDS NIH HHS/United States
GR  - R01 CA74145/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Bacterial Toxins)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (Exotoxins)
RN  - 0 (Interleukin-13 Receptor alpha2 Subunit)
RN  - 0 (Proto-Oncogene Proteins c-fos)
RN  - 0 (Virulence Factors)
RN  - 0 (fos-related antigen 1)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
RN  - EC 2.7.10.1 (Receptor, EphA2)
SB  - IM
MH  - ADP Ribose Transferases/pharmacology
MH  - Animals
MH  - Antineoplastic Agents/pharmacology
MH  - Astrocytoma/*metabolism/pathology
MH  - Bacterial Toxins/pharmacology
MH  - Biomarkers, Tumor/*analysis
MH  - Blotting, Western
MH  - Brain Neoplasms/*metabolism/pathology
MH  - Cells, Cultured
MH  - Exotoxins/pharmacology
MH  - Humans
MH  - Immunohistochemistry
MH  - Interleukin-13 Receptor alpha2 Subunit/*biosynthesis
MH  - Mice
MH  - Proto-Oncogene Proteins c-fos/*biosynthesis
MH  - Receptor, EphA2/*biosynthesis
MH  - Tissue Array Analysis
MH  - Virulence Factors/pharmacology
MH  - Pseudomonas aeruginosa Exotoxin A
EDAT- 2008/01/04 09:00
MHDA- 2008/03/28 09:00
CRDT- 2008/01/04 09:00
PHST- 2008/01/04 09:00 [pubmed]
PHST- 2008/03/28 09:00 [medline]
PHST- 2008/01/04 09:00 [entrez]
AID - 14/1/199 [pii]
AID - 10.1158/1078-0432.CCR-07-1990 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2008 Jan 1;14(1):199-208. doi: 10.1158/1078-0432.CCR-07-1990.