In breast cancer, vasoactive intestinal peptide (VIP) is an autocrine growth factor. Here the effects of pituitary adenylate cyclase activating polypeptide (PACAP) were investigated. 125I-PACAP-27 bound with high affinity (Kd = 5 nM) to T47D breast cancer cells.Specific 125I-PACAP-27 binding was inhibited with high affinity by PACAP-27, PACAP-38 and PACAP(6-38) but not PACAP(28-38). PACAP-27 elevated the cAMP and c-fos mRNA in T47D cells and the increase in cAMP was antagonized by inhibited by PACAP(6-38). PACAP(6-38) inhibited colony formation using a soft agar assay and inhibited breast cancer xenograft growth in nude mice. These results suggest that PACAP(6-38) functions as a breast cancer PACAP receptor antagonist.In prostate cancer, sigma receptor benzamides were used to image tumors. 4(125I)iodo-N-(2- (1=piperidinyl)ethyl)benzamide, 2-(125I)-N-(N-benzylpiperidin-4-yl)-2- iodobenzamide and 2-(125I)-N-(2-(1=piperidinyl)ethyl)-4-methoxy-3- trimethyl stannyl-banzamide (PIMBA) localized to DU-145 xenografts in nude mice. 125I-PIMBA bound with high affinity to DU-145 cells (Kd = 5 nM) and specific 125I-PIMBA binding was inhibited with high affinity by traditional sigma receptor ligands such as BD1008 or haloperidol (IC50 values of 0.6 and 15 nM). Also PIMBA inhibited colony formation of DU- 145, LNCaP or PC-3 cells. These results indicate that PIMBA may be useful at inhibiting prostate cancer growth in addition to localizing tumors. - VIP, PACAP, breast cancer, sigma receptors, PIMBA, - Human Tissues, Fluids, Cells, etc.
