Effects of vasoactive intestinal peptide (VIP) and somatostatin (SST) on lipoprotein receptor expression by A431 tumor cells

A variety of tumor cells have been shown to express lipoprotein receptors. Recent data suggest that lipoprotein receptors may play a regulatory role i n the growth of certain tumor cells. We investigated the effects of vasoact ive intestinal peptide (VIP) and somatostatin-14 (SsT-14) on the binding of (111)Indium-labeled lipoproteins [In-111-low density lipoprotein (In-111-L DL), In-111-high density lipoprotein (In-111-HDL) and In-111-very low densi ty lipoprotein (In-111-VLDL)] onto the epidermoid mammary carcinoma cell li ne A431. Scatchard analyses of the binding data indicated one class of spec ific high affinity binding sites for LDL, HDL and VLDL expressed by A431 ce lls, respectively. VIP increased significantly the binding capacity for In- 111-LDL on A431 cells. The VIP - induced increase of In-111-LDL binding sit es was inhibited by SST-14. Furthermore, SST-14 inhibited VIP-induced H-3-t hymidine incorporation and adenosine 3'-5' cyclic monophosphate (cAMP) form ation in A431 cells with IC,, values in the range of 5-7 nM. However, SST-1 4 showed no effect on dibutyryl-cAMP-induced increase of In-111-LDL binding sites expressed on A431 cells. In contrast to In-111-LDL binding, no effec ts of VIP or SST-14 on HDL or VLDL binding to A431 tumor cells were found. Our results suggest a direct effect of VIP and SST-14 on LDL-binding onto t umor cells. The complex interactions between VIP and SST-14 on LDL receptor expression of tumor cells may play a role in tumor cell lipid metabolism. (C) 2001 Elsevier Science Inc. All rights reserved.