The effects of
vasoactive intestinal peptide (VIP) on the proliferation of central nervous system (CNS) and
cancer cells were investigated. VIP has important actions during CNS development. During neurogenesis, VIP stimulates the proliferation and differentiation of brain neurons. Addition of VIP to embryonic mouse spinal cord cultures increases neuronal survival and
activity dependent neurotrophic factor (ADNF) secretion from astroglial cells. VIP is an integrative regulator of brain growth and development during neurogenesis and embryogenesis. Also, VIP causes increased proliferation of human breast and
lung cancer cells in vitro. VIP binds with high affinity to
cancer cells, elevates the cAMP and increases gene expression of c-fos, c-jun, c-myc and vascular endothelial cell
growth factor. The effects of VIP on
cancer cells are reversed by VIPhybrid, a synthetic VPAC(1) receptor antagonist.
VIPhyb inhibits the basal growth of
lung cancer cells in vitro and
tumors in vivo and potentiates the ability of chemotherapeutic drugs to kill
cancer cells. Due to the high density of VPAC(1) receptors in
cancer cells, VIP has been radiolabeled with 123I, 18F and 99mTc to image
tumors. It remains to be determined if radiolabeled VIP analogs will be useful agents for early detection of
cancer in patients.