TY - JOUR
T1 - Inhibition of human neuroblastoma growth by a specific VIP antagonist
AU - Lilling, G.
AU - Wollman, Y.
AU - Goldstein, M. N.
AU - Rubinraut, S.
AU - Fridkin, M.
AU - Brenneman, D. E.
AU - Gozes, I.
PY - 1994/1
Y1 - 1994/1
N2 - The 28-amino-acid neuropeptide, vasoactive intestinal peptide (VIP), is a potent mitogen during embryonic development and plays a vital role in brain growth. VIP is also mitogenic for tumor cells, including the human neuroblastoma (NMB). Northern blot analysis has revealed VIP mRNA transcripts in NMB. We now report VIP-like immunoreactivity within these neuroblastoma cells that increased during logarithmic growth and decreased after attaining confluency. About 106 seeded cells secreted 5-40 pg of VIP-like immunoreactivity into the medium. These results suggest an autocrine role for VIP in the regulation of neuroblastoma growth. A VIP hybrid antagonist (neurotensin6-11 VIP7-28) that has been shown to inhibit lung cancer proliferation was now tested for inhibition of neuroblastoma growth. Receptor binding studies indicated that the hybrid antagonist displaced [125I]-VIP binding in the neuroblastoma cells (EC50=5×10-6 M). Furthermore, as measured by thymidine incorporation and by cell counts, the potent VIP hybrid antagonist inhibited neuroblastoma multiplication in a dose-dependent manner. In conclusion, VIP may be an important regulator of growth of nerve cell progenitors and of tumors derived from neuronal origin and intervening with VIP function may lead to improved treatment of cancer.
AB - The 28-amino-acid neuropeptide, vasoactive intestinal peptide (VIP), is a potent mitogen during embryonic development and plays a vital role in brain growth. VIP is also mitogenic for tumor cells, including the human neuroblastoma (NMB). Northern blot analysis has revealed VIP mRNA transcripts in NMB. We now report VIP-like immunoreactivity within these neuroblastoma cells that increased during logarithmic growth and decreased after attaining confluency. About 106 seeded cells secreted 5-40 pg of VIP-like immunoreactivity into the medium. These results suggest an autocrine role for VIP in the regulation of neuroblastoma growth. A VIP hybrid antagonist (neurotensin6-11 VIP7-28) that has been shown to inhibit lung cancer proliferation was now tested for inhibition of neuroblastoma growth. Receptor binding studies indicated that the hybrid antagonist displaced [125I]-VIP binding in the neuroblastoma cells (EC50=5×10-6 M). Furthermore, as measured by thymidine incorporation and by cell counts, the potent VIP hybrid antagonist inhibited neuroblastoma multiplication in a dose-dependent manner. In conclusion, VIP may be an important regulator of growth of nerve cell progenitors and of tumors derived from neuronal origin and intervening with VIP function may lead to improved treatment of cancer.
KW - VIP hybrid antagonist
KW - Vasoactive intestinal peptide
KW - autocrine growth factor
KW - mitogenic factor
KW - neuroblastoma
KW - neurotensin-VIP
UR - http://www.scopus.com/inward/record.url?scp=0028700369&partnerID=8YFLogxK
U2 - 10.1007/BF02736724
DO - 10.1007/BF02736724
M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???
AN - SCOPUS:0028700369
SN - 0895-8696
VL - 5
SP - 231
EP - 239
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
IS - 4
ER -
