Effect of ploidy, recruitment, environmental factors, and tamoxifen treatment on the expression of sigma-2 receptors in proliferating and quiescent tumour cells

Abstract

Summary 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.

Rapid Reduction of 1-Receptor Binding and 18F-FDG Uptake in Rat Gliomas After In Vivo Treatment with Doxorubicin

“…Expression of both subtypes of s-receptors in tumor cells and in solid tumors is related to cellular proliferation (3,10,11). A recent study on a large number of human cell lines showed that cancer cells express much higher levels of s 1 -receptors than do corresponding noncancerous cells (3).…”

Imaging the Sigma-2 Receptor for Diagnosis and Prediction of Therapeutic Response

“…The density of σ 2 receptors in the 66P cells was found to be quite high, ~900,000 copies/cell versus ~90,000 receptors/cell in the 66Q cells. This group also reported that the expression kinetics of σ 2 receptors follows the growth kinetics of the 66 cells ( Figure 1B) [15]. A subsequent study in solid tumor xenografts of the same tumor cell lines demonstrated the identical P:Q ratio to that measured in the cell culture condition [16].…”

Evaluation of Radioiodinated 1-[2-(3,4-Dimethoxyphenyl)ethyl]-4-(2-iodophenylpropyl)piperazine as a Tumor Diagnostic Agent with Functional Sigma Receptor Imaging by Single Photon Emission Computed Tomography

“…18,23,29) As an initial screening to assess the relative potential The expression of sigma receptors in various tumors may serve as a better biomarker of a tumor's proliferative status. [14][15][16] In vitro studies of tumor cells in a proliferative state showed an 8-10 times higher sigma receptor density than tumor cells in a quiescent state. 16) Expression of the sigma receptors parallels the proliferative status of breast tumors implanted in nude mice.…”