Mistletoe lectin binds to multidrug resistance-associated protein MRP5.

BACKGROUND: Mistletoe lectins (MLs) are the active components of aqueous mistletoe extracts widely used in complementary cancer therapy, however, it is not clear if they bind to carbohydrate residues only or whether they interact with proteins as well. Protein-protein interactions do not seem unlikely as MLs act at very low molar concentrations usually observed with peptide-peptide interactions only and not seen with lectin-sugar interactions. MATERIALS AND METHODS: In order to detect protein-protein interactions a random peptide library was screened for the ability to bind to MLs. RESULTS: MLs bound to peptides showing homologies to multidrug resistance-associated protein 5 (MRP5). However, the MLs only slightly modified the MRP5 efflux pump, while periodate treatment to inhibit cell membrane binding via glycan completely abolished the ML-I binding sites in MRP5 overexpressing cells. CONCLUSION: The protein sequence is not important for ML-I binding, indicating that the biological activity of MLs can most likely be attributed to the sugar chains.

Hyaluronate and its receptors in bone marrow.

Cell-cell and cell-matrix interactions, which are mediated by cell adhesion molecules, play a fundamental role during many cellular processes including growth, differentiation, cell migration and cancer metastasis. One molecule playing a major role in these processes is the CD44 surface receptor, which is expressed in a wide range of cells including many cells of the hemopoietic system, where it mediates the interaction with its major ligand, hyaluronate. However, little is known about CD44 and hyaluronate in bone marrow and this was investigated immunohistochemically in trephine biopsies and in cultivated human bone marrow stromal cells. In biopsy specimens, patches of hyaluronate deposition were detected in the extracellular matrix (ECM). However, most of the areas of the ECM were devoid of hyaluronate. Single mast cells and lymphocytes scattered throughout the marrow were CD44 immunopositive. Marrow-derived stromal cells (MDSC) expanded in cell culture were immunopositive for CD44, hyaluronate synthase, and hyaluronate. Hence, a marked difference between CD44 immunolocalisation and hyaluronate deposition can be observed between in situ and under cell culture conditions. Since in normal marrow in situ the number of CD44 immunopositive cells was low, interactions of CD44 and hyaluronate would appear to not to play a major role in cell adhesion in the normal bone marrow.