THE MONOCLONAL ANTI-CYTOKERATIN-8 ANTIBODY, 6D7, TARGETS QUIESCENT CELLS IN PROSTATIC-CARCINOMA SPHEROIDS

A monoclonal antibody, 6D7, reactive with cytokeratin-8, the most abun dant type of cytokeratin in normal and malignant epithelial cells, was examined for its binding in DU 145 prostatic carcinoma spheroids. It was found that 6D7 bound in the intermediate, quiescent cell layers of the spheroids while no binding was observed either in the outer layer s, which comprises mainly proliferating cells, or in the central necro tic core of the spheroids. Even within the quiescent cell layers, bind ing was only observed in certain cells that appeared to have incorpora ted the anticytokeratin antibody. It is likely that these cells had a disturbance in cell membrane permeability and therefore permitted the transmembrane passage of 6D7. The disturbed cell membrane permeability was due to the local environmental conditions in the spheroids, since quiescent monolayer cells did not incorporate 6D7. A complementary bi nding of 6D7 and E4, a prostatic carcinoma reactive monoclonal antibod y, was found in the DU 145 spheroids. While E4 bound strongly in the o uter viable cell layers, 6D7 bound in the quiescent cell layers close to the necrotic core. A combination of radiolabelled 6D7 and E4, there fore appears efficient in targeting both proliferating and quiescent c ells.