Bombesin and bombesin antagonists: studies in Swiss 3T3 cells and human small cell lung cancer.
Bombesins are potent growth factors for murine Swiss 3T3 cells. Using these cells in chemically defined conditions we have been able to characterise the bombesin receptor and the early signals preceding DNA synthesis. We describe two substance P analogues [DArg1, DPro2, DTrp7,9, Leu11] substance P and [DArg1, DPhe5, DTrp7,9, Leu11] substance P which competitively block the binding of bombesins to their receptor and all the events leading to mitogenesis. Bombesins are secreted by human small cell lung cancers (SCLC) and may act as autocrine growth factors for these tumours, so the development of peptide bombesin antagonists could have therapeutic implications. We demonstrate that the antagonists can reversibly inhibit the growth of SCLC in vitro, with relatively little effect on other lung tumours.
Woll
P J
PJ
Imperial Cancer Research Fund, Lincoln's Inn Fields, London, UK.
Rozengurt
E
E
D000818:Animals; D001839:Bombesin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D018288:Carcinoma, Small Cell / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008815:Mice, Inbred Strains; D008938:Mitosis; D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter / Q000032:analysis; D014407:Tumor Cells, Cultured / Q000187:drug effects
D018004:Receptors, Bombesin; D017981:Receptors, Neurotransmitter; D001839:Bombesin