Decreasing expression of the interleukin-13 receptor IL-13Ralpha2 in treated recurrent malignant gliomas.
The IL-13Ralpha2 gene encodes for a 65 kDa protein that forms one of the subunits of the interleukin-13 (IL-13) receptor. This gene is highly expressed in various types of human tumors including malignant gliomas. The expression level of IL-13Ralpha2 was examined in a total of 45 tissue samples of anaplastic astrocytomas (AAs) World Health Organization (WHO) grade III, glioblastomas (GBMs) WHO grade IV, and first-recurrent glioblastomas (frGBMs) after treatment with radiation and chemotherapy. IL-13Ralpha2 expression was detected by semiquantitative reverse transcription real-time polymerase chain reaction (PCR) using ABI PRISM 7700 and Qiagen QuantiTect SYBR Green PCR kits. The expression level of IL-13Ralpha2 (15 fold) was significantly reduced in frGBMs compared to the primary GBMs (p = 0.014), and significantly reduced by more than 15 fold (p = 0.003) in all untreated malignant astrocytomas (AAs and GBMs) compared with treated frGBMs. Expression of IL-13Ralpha2 seems to be lower in frGBMs compared to GBMs. The promising antitumor effect of IL-13 cytotoxin could be greatly reduced in frGBM or only achievable with higher amounts of cytotoxin, due to the significantly lower expression of the cytotoxin's target structure.
Bozinov
Oliver
O
Department of Neurosurgery, University Hospital Zürich, Switzerland. oliver.bozinov@usz.ch
Kalk
Jens-Martin
JM
Krayenbühl
Niklaus
N
Woernle
Christoph Michael
CM
Sure
Ulrich
U
Bertalanffy
Helmut
H
D000199:Actins / Q000235:genetics / Q000378:metabolism; D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D005098:Exotoxins / Q000627:therapeutic use; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology / Q000628:therapy; D006801:Humans; D000922:Immunotoxins / Q000627:therapeutic use; D018793:Interleukin-13 / Q000627:therapeutic use; D053663:Interleukin-13 Receptor alpha2 Subunit / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000378:metabolism* / Q000473:pathology; D015376:Nimustine / Q000008:administration & dosage; D012313:RNA / Q000032:analysis; D011993:Recombinant Fusion Proteins; D013713:Teniposide / Q000008:administration & dosage; D055815:Young Adult
D000199:Actins; D005098:Exotoxins; C521502:IL13-PE38; D000922:Immunotoxins; D018793:Interleukin-13; D053663:Interleukin-13 Receptor alpha2 Subunit; D011993:Recombinant Fusion Proteins; D015376:Nimustine; D012313:RNA; D013713:Teniposide