Gastrin releasing peptide-preferring bombesin receptors mediate growth of human renal cell carcinoma.
Bombesin-like peptides typically act as neurotransmitters along the brain-gut axis and as growth factors in various human tissues. The present study demonstrates the expression of gastrin releasing peptide (GRP)-preferring bombesin receptors in human renal cell carcinoma but not in normal kidney tissue. The expression of GRP receptors was characterized at the mRNA level by reverse transcription-PCR, as well as at the protein level by binding of (125)I-[Tyr(4)] bombesin to membranes prepared from tumor tissue (K(d) 0.3 nM) and healthy kidney tissue from the same four patients. GRP receptors were also demonstrated in four human kidney carcinoma cell lines (A-498, CAKI-1, CAKI-2, and ACHN). The effects of bombesin/GRP agonists and/or antagonists on growth were investigated in vitro on CAKI-2 cells, which expressed large amounts of GRP receptors. Cell numbers stimulated by 10% fetal calf serum were significantly stimulated by interleukin-1beta (control) and GRP-7 (10(-7) M), both in the range of 136 to 148%; addition of the GRP receptor antagonist acetyl-GRP(20-27) (10(-6) M) completely reversed this effect. Bombesin alone (10(-6) M) significantly stimulated CAKI-2 cells (129%) cultured with 0.5% fetal calf serum, whereas another antagonist, D-Phe6,Leu13,(CH2NH)Leu14 bombesin(6-14) (1 microM), alone did not inhibit growth, thus excluding an autocrine mechanism. These results indicate for the first time that malignant transformation of human kidney tissue into renal cell carcinoma is accompanied by novel expression of GRP receptors. Bombesin-like peptides might act as mitogens in these carcinomas, and they might be useful as diagnostic or therapeutic tools such as tumor imaging or internal radiotherapy.
Pansky
Andreas
A
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
DE Weerth
Andreas
A
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Fasler-Kan
Elizaveta
E
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
Boulay
Jean-Louis
JL
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
Schulz
Martina
M
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Ketterer
Sylvia
S
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
Selck
Cristin
C
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Beglinger
Christoph
C
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
VON Schrenck
Tammo
T
Medizinische Kernklinik und Poliklinik, Universitäts-Krankenhaus Eppendorf, Hamburg, Germany.
Hildebrand
Pius
P
Department of Research and Division of Gastroenterology, University Hospital, Basel, Switzerland.
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000818:Animals; D001839:Bombesin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D019556:COS Cells; D002292:Carcinoma, Renal Cell / Q000378:metabolism / Q000473:pathology*; D002455:Cell Division / Q000502:physiology; D005260:Female; D019886:Gastrin-Releasing Peptide / Q000378:metabolism*; D006801:Humans; D007680:Kidney Neoplasms / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000378:metabolism; D018004:Receptors, Bombesin / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D014407:Tumor Cells, Cultured
D012333:RNA, Messenger; D018004:Receptors, Bombesin; D019886:Gastrin-Releasing Peptide; D001839:Bombesin