Neuropeptides as autocrine growth factors in cancer cells.
Neuropeptides can function as autocrine growth factors in cancer cells. High levels of bombesin (BB) and neurotensin (NT)-like immunoreactivity are present in small cell lung cancer (SCLC), a neuroendocrine tumor. Vasoactive intestinal peptide (VIP) stimulates and somatostatin (SST) inhibits the release of BB-like peptides from SCLC cells. BB-like peptides bind to BB(2) receptors, which are present on the cell surface. BB-like peptides stimulate the mitogen activated protein kinase (MAPK) cascade leading to increased expression of nuclear oncogenes and growth factors in SCLC cells. Due to the high density of neuropeptide receptors present on the cell surface, SST analogs have been radiolabeled to image neuroendocrine tumors. VIP receptors are present in many epithelial cancers including breast, colon, non-small cell lung cancer (NSCLC), pancreatic and prostate cancers. Due to the high density of VIP receptors on lung cancer cells, radiolabeled VIP agonists may be used to image these tumors. VIP receptor antagonists, such as VIPhybrid, inhibit the growth of cancer cell lines in vitro and in vivo. VIPhybrid and SR48692, a NT receptor antagonist, potentiate the cytotoxicity of chemotherapeutic drugs. These results suggest that neuropeptide receptor antagonists may be useful in the treatment of cancer.
Moody
Terry W
TW
Office of the Director, CCR, National Cancer Institute, Bethesda, MD 20892, USA. moodyt@mail.nih.gov
Chan
Daniel
D
Fahrenkrug
Jan
J
Jensen
Robert T
RT
D019898:Autocrine Communication; D018278:Carcinoma, Neuroendocrine / Q000188:drug therapy* / Q000378:metabolism; D018288:Carcinoma, Small Cell / Q000188:drug therapy* / Q000378:metabolism; D006133:Growth Substances / Q000627:therapeutic use; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism / Q000627:therapeutic use*; D018013:Receptors, Neuropeptide / Q000187:drug effects* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D006133:Growth Substances; D009479:Neuropeptides; D018013:Receptors, Neuropeptide