Recently, we demonstrated that
sigma-2 receptors may have the potential to be a
biomarker of tumour cell proliferation (Mach et al (1997)
Cancer Res 57: 156-161). If
sigma-2 receptors were a
biomarker of tumour cell proliferation, they would be amenable to detection by non-invasive imaging procedures, thus eliminating many of the problems associated with the flow cytometric measures of tumour cell proliferation presently used in the clinic. To be a good
biomarker of tumour cell proliferation, the expression of
sigma-2 receptors must be essentially independent of many of the
biological, physiological, and/or environmental properties that are found in solid tumours. In the investigation reported here, the mouse mammary
adenocarcinoma lines, 66 (diploid) and 67 (
aneuploid), 9L rat brain tumour cells, and MCF-7 human breast tumour cells were used to study the extent and kinetics of expression of
sigma-2 receptors in proliferative (P) and quiescent (Q) tumour cells as a function of species, cell type, ploidy, pH, nutrient depletion, metabolic state, recruitment from the Q-cell compartment to the P-cell compartment, and treatment with
tamoxifen. In these experiments, the expression of
sigma-2 receptors solely reflected the proliferative status of the tumour cells. None of the
biological, physiological, or environmental properties that were investigated had a measurable effect on the expression of
sigma-2 receptors in these model systems. Consequently, these data suggest that the proliferative status of tumours and normal tissues can be non-invasively assessed using radiolabelled
ligands that selectively bind
sigma-2 receptors.