Luteinizing hormone releasing hormone-RNase A conjugates specifically inhibit the proliferation of LHRH-receptor-positive human prostate and breast tumor cells

Abstract

Human prostate and breast tumor cells produce luteinizing hormone-releasing hormone (LHRH) receptors on their cell surface even when they have lost dependency on sex steroid hormones for growth. To investigate whether LHRH can be used as a cell-binding moiety to deliver toxin molecules into prostate and breast tumor cells, LHRH-bovine RNase A conjugates were constructed using the chemical crosslinking method. The treatment of the LHRH receptor-positive cells such as prostate LNCapFGC and breast MCF7 tumor cells with LHRH-RNase A conjugates resulted in a dose-dependent inhibition of growth. The cytotoxic activities of these conjugates were effectively reduced by the presence of exogenous LHRH. Either free RNase A or LHRH alone did not affect the proliferation of these cells. The LHRH-RNase A conjugates did not show cytotoxicity against FRTL5 and TM4 cells which do not express the LHRH receptors, These results suggest that LHRH can be used as a cell-binding molecule for the specific delivery of toxin molecules into the cells which express LHRH receptors on their surface. Thus, a new class of biomedicines that act as fusion proteins between LHRH and toxins will give us a new avenue for the treatment of human prostate and breast cancers, regardless of their steroid hormone dependency.