VARYING SENSITIVITY OF HUMAN MAMMARY-CARCINOMA CELLS TO THE TOXIC EFFECT OF PARVOVIRUS H-1

We have previously demonstrated lysis of non-established cultures of h uman mammary carcinoma cells by parvovirus H-l, which has little effec t on the proliferation of corresponding normal cultures. In the presen t study, we examined this effect in a number of breast-tumour specimen s and found them to differ as to the amplitude of their response to pa rvoviral attack. We first investigated whether the differences in cell sensitivity to parvovirus infection reflected the differentiation lev el of the initial tumour. Among the biochemical and anatomopathologica l indicators of original tumour differentiation, the presence of oestr ogenic receptors (ER) was found to have a predictive value as to the s ensitivity of derived cultures to the cytopathic effect of H-1 virus. The ER+ tumour-derived cultures showed an incresed sensitivity to the lytic effect of H-l virus compared with the ER+ tumour-derived culture s, in spite of similar average proliferation rates for the two types o f cultures. The proliferation rate was more heterogeneous among ER+ tu mour-derived cultures and, in this group, the faster growing cultures were also the most sensitive. This observation was corroborated by the study of established cell lines retaining ER expression under in vitr o culture conditions. Oestradiol was found to increase the sensitivity of these cells to the parvovirus in parallel with induction of prolif eration. This effect appeared to be mediated by ER activation, since i t was not observed in the ER-negative cell line MDA-MB-231. These data point to the importance of hormonal influences and cellular parameter s, notably differentiation and proliferation, in determining the exten t to which human cancer cells can be targets for the cytopathic effect of parvoviruses. (C) 1997 Elsevier Science Ltd.