PMID- 7812973
OWN - NLM
STAT- MEDLINE
DCOM- 19950203
LR  - 20220408
IS  - 0008-5472 (Print)
IS  - 0008-5472 (Linking)
VI  - 55
IP  - 2
DP  - 1995 Jan 15
TI  - Sigma-1 and sigma-2 receptors are expressed in a wide variety of human and rodent 
      tumor cell lines.
PG  - 408-13
AB  - Thirteen tumor-derived cell lines of human and nonhuman origin and from various 
      tissues were examined for the presence and density of sigma-1 and sigma-2 
      receptors. Sigma-1 receptors of a crude membrane fraction were labeled using 
      [3H](+)-pentazocine, and sigma-2 receptors were labeled with 
      [3H]1,3-di-o-tolylguanidine ([3H]DTG); in the presence or absence of 
      dextrallorphan. [3H](+)-Pentazocine-binding sites were heterogeneous. In rodent 
      cell lines (e.g., C6 glioma, N1E-115 neuroblastoma, and NG108-15 neuroblastoma x 
      glioma hybrid), human T47D breast ductal carcinoma, human NCI-H727 lung 
      carcinoid, and human A375 melanoma, [3H](+)-pentazocine bound to high- and 
      low-affinity sites with Kd1 = 0.67-7.0 nM, Bmax1 = 25.5-108 fmol/mg protein, Kd2 
      = 127-600 nM, and Bmax2 = 942-5431 fmol/mg protein. However, [3H](+)-pentazocine 
      bound to a single site in other cell lines. In human U-138MG glioblastoma, 
      SK-N-SH neuroblastoma, and LNCaP.FGC prostate, Kd = 28-61 nM and Bmax = 975-1196 
      fmol/mg protein, whereas in ThP-1 leukemia Kd = 146 nM and Bmax = 1411 fmol/mg 
      protein. The sigma-1-like nature of [3H](+)-pentazocine-binding sites was 
      confirmed by competition studies which revealed high affinity for haloperidol and 
      enantioselectivity for (+)-pentazocine over (-)-pentazocine. Interestingly, human 
      MCF-7 breast adenocarcinoma showed little or no specific binding of 
      [3H](+)-pentazocine, suggesting the absence of sigma-1 receptors in this cell 
      line. All cell lines examined expressed a high density of sigma-2 receptors with 
      Kd values for [3H]DTG ranging from 20 to 101 nM and Bmax values of 491 to 7324 
      fmol/mg protein. Competition studies indicated possible heterogeneity of sigma-2 
      receptors. While sites labeled by [3H]DTG in all cell lines tested exhibited 
      affinity for haloperidol and preference for (-)-pentazocine over the 
      (+)-enantiomer, human cell lines generally showed 4- to 7-fold lower affinity for 
      haloperidol and approximately 10-fold lower affinity for (-)-pentazocine compared 
      with the rodent cell lines. The high density of sigma-1 and sigma 2-binding sites 
      in these cell lines suggests important cellular functions in cancer, as well as 
      potential diagnostic utility for tumor-imaging agents which target sigma sites. 
      These cell lines may be useful as model systems in which to study the functions 
      of sigma sites in normal tissues, as well as their possible role in tumor 
      biology.
FAU - Vilner, B J
AU  - Vilner BJ
AD  - Unit on Receptor Biochemistry and Pharmacology, National Institute of Diabetes 
      Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 
      20892.
FAU - John, C S
AU  - John CS
FAU - Bowen, W D
AU  - Bowen WD
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Cancer Res
JT  - Cancer research
JID - 2984705R
RN  - 0 (Guanidines)
RN  - 0 (Receptors, sigma)
RN  - J6292F8L3D (Haloperidol)
RN  - RP4A60D26L (Pentazocine)
SB  - IM
MH  - Adenocarcinoma/metabolism
MH  - Animals
MH  - Binding, Competitive
MH  - Breast Neoplasms/metabolism
MH  - Carcinoma, Ductal, Breast/metabolism
MH  - Glioblastoma/metabolism
MH  - Guanidines/metabolism
MH  - Haloperidol/metabolism
MH  - Humans
MH  - Leukemia/metabolism
MH  - Lung Neoplasms/metabolism
MH  - Male
MH  - Melanoma/metabolism
MH  - Mice
MH  - Neuroblastoma/metabolism
MH  - Pentazocine/metabolism
MH  - Prostatic Neoplasms/metabolism
MH  - Receptors, sigma/*metabolism
MH  - Tumor Cells, Cultured/*metabolism
EDAT- 1995/01/15 00:00
MHDA- 1995/01/15 00:01
CRDT- 1995/01/15 00:00
PHST- 1995/01/15 00:00 [pubmed]
PHST- 1995/01/15 00:01 [medline]
PHST- 1995/01/15 00:00 [entrez]
PST - ppublish
SO  - Cancer Res. 1995 Jan 15;55(2):408-13.