Specific sensitivity of small cell lung cancer cell lines to the snake venom toxin taipoxin.
Small cell lung cancer (SCLC) is a malignant disease, for which no satisfactory treatment is presently available and consequently, new specific therapeutic targets are in high demand. A global gene expression analysis previously performed, identified the neuronal pentraxin receptor (NPR) as highly and relatively specifically expressed in SCLC, consistent with the neuroendocrine features of this cancer. Normally, NPR is exclusively expressed in neurons, where it associates with the homologous proteins neuronal pentraxins 1 and 2 (NP1 and NP2) in complexes capable of binding the snake venom neurotoxin taipoxin. The purpose of the present study was to assess the toxic effect of taipoxin in SCLC-cell lines and to determine if toxicity correlates to NPR and NP1 and NP2 expression levels. NPR was detected by Western blot analysis in all the tested SCLC and in control cell lines of different origin. The receptor co-purified with cell membrane in SCLC, indicating that NPR is surface associated. Microarray signals for NP1 and NP2mRNA was detected in a subset of SCLC-cell lines and validated by Northern blot analysis. Furthermore, NP1 protein was detected by Western blot analysis in a few SCLC-cell lines, but not in the control cell lines. A number of SCLC-cell lines showed marked sensitivity to taipoxin (IC50: 3-130 nM) at toxin concentrations leaving the control cell lines unaffected. The sensitivity to taipoxin did not correlate with the expression levels of NP1 protein and NP2-mRNA, suggesting that expression of these proteins may not be required for taipoxin induced toxicity in SCLC. The demonstrated toxic effect of taipoxin in SCLC may prove to be of importance for designing novel specific treatment modalities for this disease.
Poulsen
Thomas T
TT
Department of Radiation Biology, Section 6321, Finsen Center, National University Hospital, Blegdamsvej 9, 2100 Copenhagen Ø, Denmark.
Pedersen
Nina
N
Perin
Mark S
MS
Hansen
Celia K
CK
Poulsen
Hans S
HS
D015152:Blotting, Northern; D015153:Blotting, Western; D002097:C-Reactive Protein / Q000235:genetics / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D045744:Cell Line, Tumor; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D004546:Elapid Venoms / Q000494:pharmacology* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D000099153:Pentraxins
D002097:C-Reactive Protein; D004273:DNA, Neoplasm; D004546:Elapid Venoms; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D000099153:Pentraxins; C015523:taipoxin