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

Over the past several years, our group has provided considerable evidence t hat the expression of sigma-2 (sigma(2)) receptors may serve as a biomarker of tumour cell proliferation. In these in vitro studies, sigma(2) receptor s 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 environmenta l factors often found in solid rumours. Moreover, the expression of sigma(2 ) 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. H owever, these in vitro studies may or may not be indicative of what might o ccur in solid tumours. In the present study, the sigma(2) receptor P:Q rati o was determined for the cells from subcutaneous 66 (diploid) and 67 (aneup loid) rumours grown in female nude mice. The sigma(2) receptor P:Q ratio of the 66 tumours was 10.6 compared to the sigma(2) receptor P:Q ratio of 9.5 measured for the 66 tissue culture model. The sigma(2) receptor P:Q ratio of the 67 tumours was 4.5 compared to the sigma(2) receptor 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 sigma (2) receptors may be a reliable biomarker of the proliferative status of so lid tumours and (2) radioligands with both high affinity and high selectivi ty for sigma(2) receptors may have the potential to non-invasively assess t he proliferative status of human solid rumours using imaging techniques suc h as positron emission tomography or single-photon emission computerized to mography. (C) 2000 Cancer Research Campaign.