Sigma-2 receptors as a biomarker of proliferation in solid tumours

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Abstract
Over the past several years, our group has provided considerable evidence that the expression of sigma-2 (σ2) receptors may serve as a biomarker of tumour cell proliferation. In these in vitro studies, σ2receptors 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 σ2receptors 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 σ2receptor P:Q ratio was determined for the cells from subcutaneous 66 (diploid) and 67 (aneuploid) tumours grown in female nude mice. The σ2receptor P:Q ratio of the 66 tumours was 10.6 compared to the σ2receptor P:Q ratio of 9.5 measured for the 66 tissue culture model. The σ2receptor P:Q ratio of the 67 tumours was 4.5 compared to the σ2receptor P:Q ratio of ≈ 8 measured for the 67 tissue culture model. The agreement between the solid tumour and tissue culture data indicates that: (1) the expression of σ2receptors may be a reliable biomarker of the proliferative status of solid tumours and (2) radioligands with both high affinity and high selectivity for σ2receptors 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. © 2000 Cancer Research Campaign

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