Expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in a human renal cell carcinoma cell line, VMRC-RCW

Abstract

Background. The kidney produces and secretes various vasoactive peptides, such as endothelin-1 and adrenomedullin, and expresses receptors for these peptides. These vasoactive peptides are considered to have autocrine or paracrine growth-regulatory activities in the kidney, in addition to actions in the renal circulation, and water and electrolyte transport. It was reported that renal cell carcinoma cell lines, such as VMRC-RCW cells, secreted some autocrine growth factors. The production of these peptides by VMRC-RCW cells has not been studied, however. Methods. We studied the expression of three vasoactive peptides, urotensin-II, adrenomedullin, and endothelin-1, in VMRC-RCW human renal cell carcinoma cells by radioimmunoassay, Northern blot analysis, and reverse transcriptase polymerase chain reaction (RT-PCR). Results. Northern blot analysis showed the expression of adrenomedullin mRNA in VMRC-RCW cells. RT-PCR analysis showed the expression of urotensin-II and endothelin-1 mRNAs in VMRC-RCW cells. Immunoreactive adrenomedullin and immunoreactive endothelin were detected in the culture medium (17.5 ± 0.70 fmol/105 cells per 24 h, and 0.75 ± 0.03 fmol/105 cells per 24 h, respectively, mean ± SEM; n = 6). The adrenomedullin levels in the medium were higher in VMRC-RCW cells than in DLD-1 colonic carcinoma cells and HeLa cervical cancer cells, but the endothelin levels were lower in VMRC-RCW cells. Reverse-phase high performance liquid chromatogra-phy suggested that VMRC-RCW cells secreted both endothelin-1 and endothelin-2. On the other hand, no significant amount of urotensin-II was detected in the culture medium (<0.5 fmol/105 cells per 24 h). Conclusions. VMRC-RCW human renal cell carcinoma cells express three vasoactive peptides; urotensin-II, adrenomedullin, and endothelin-1. The secreted peptides may be related to tumor biology as well as renal pathophysiology.