Human renal cell cancer proliferation in tissue culture is tonically inhibited by opioid growth factor

Purpose: Peptide growth factors alter cellular events by binding to specifi c receptors. One group of peptides, the endogenous opioids, is important in the growth of normal and neoplastic tissue. [Met(5)]enkephalin, also terme d opioid growth factor (OGF), is a tonically active inhibitory factor that interacts with the OGF receptor, OGFr, formerly identified as Creek zeta (5 ) and appears to be autocrine produced by human cancer cells. This study ex amined the hypothesis that OGF directly inhibits proliferation of renal cel l carcinoma in tissue culture. Materials and Methods: Human renal cancer cells (Caki-2) were grown using r outine tissue culture techniques. A variety of natural and synthetic opioid s including OGF, opioid antagonists, and opioid antibodies were added to re nal cancer cell cultures to determine role of these peptides in renal cell carcinoma. The experiments were repeated in serum-free media, and with 4 ot her human renal cancer cell Lines: Caki-2, A498, SN12C, and ACHN. Immunocyt ochemistry was performed to examine the presence of OGF and its receptor. Results: OGF was the most potent opioid peptide to influence human renal ce ll carcinoma. OGF depressed growth within 12 hours of treatment,with cell n umbers subnormal by up to 48% of control levels. OGF action was receptor me diated, reversible, not cytotoxic, neutralized by antibodies to the peptide , and detected in the human renal cell carcinoma lines examined. OGF appear ed to be autocrine produced and secreted, and was constitutively expressed. Both OGF and its receptor were detected in these cells. Conclusion: OGF tonically inhibits renal cancer cell proliferation in tissu e culture, and may play a role in the pathogenesis and management of human renal cell cancer.