Sigma-2 receptors as a biomarker of proliferation in solid tumours.
Over the past several years, our group has provided considerable evidence that the expression of sigma-2 (sigma2) receptors may serve as a biomarker of tumour cell proliferation. In these in vitro studies, sigma2 receptors were expressed 8-10 times more in proliferative (P) tumour cells than in quiescent (Q) tumour cells, and the extent and kinetics of their expression were independent of a number of biological, physiological and environmental factors often found in solid tumours. Moreover, the expression of sigma2 receptors followed both the population growth kinetics when Q-cells were recruited into the P-cell compartment and the proliferative status of human breast tumour cells treated with cytostatic concentrations of tamoxifen. However, these in vitro studies may or may not be indicative of what might occur in solid tumours. In the present study, the sigma2 receptor P:Q ratio was determined for the cells from subcutaneous 66 (diploid) and 67 (aneuploid) tumours grown in female nude mice. The sigma2 receptor P:Q ratio of the 66 tumours was 10.6 compared to the sigma2 receptor P:Q ratio of 9.5 measured for the 66 tissue culture model. The sigma2 receptor P:Q ratio of the 67 tumours was 4.5 compared to the sigma2 receptor P:Q ratio of approximately equal 8 measured for the 67 tissue culture model. The agreement between the solid tumour and tissue culture data indicates that: (1) the expression of sigma2 receptors may be a reliable biomarker of the proliferative status of solid tumours and (2) radioligands with both high affinity and high selectivity for sigma2 receptors may have the potential to non-invasively assess the proliferative status of human solid tumours using imaging techniques such as positron emission tomography or single-photon emission computerized tomography.
Wheeler
K T
KT
Department of Radiology, Wake Forest University School of Medicine, Winston-Salem, NC 27157, USA.
Wang
L M
LM
Wallen
C A
CA
Childers
S R
SR
Cline
J M
JM
Keng
P C
PC
Mach
R H
RH
D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D002455:Cell Division; D005260:Female; D015674:Mammary Neoplasms, Animal / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D051379:Mice; D009361:Neoplasm Invasiveness; D011379:Prognosis; D017480:Receptors, sigma / Q000235:genetics* / Q000502:physiology; D014407:Tumor Cells, Cultured
D014408:Biomarkers, Tumor; D017480:Receptors, sigma; C106107:sigma-2 receptor