Galectin-8 enhances adhesion of multiple myeloma cells to vascular endothelium and is an adverse prognostic factor.
Multiple myeloma is characterized by abnormal infiltration of malignant plasma cells into bone marrow. Testing the hypothesis that bivalent galectin-8 (Gal-8) may influence homing of myeloma cells to vascular endothelium as a key prerequisite for infiltration, we analyzed the two Gal-8 splice variants (Gal-8S, Gal-8L). They differ in the length of their linker peptide connecting the two lectin domains. Both Gal-8 isoforms bind to cells of the myeloma lines Gal-8+MOLP-8 and Gal-8-LP-1 in a glycan-inhibitable manner. Both Gal-8 isoforms led to enhanced adhesion of myeloma cells to vascular endothelium under dynamic shear stress conditions, Gal-8L (by more than 40-fold) even stronger than Gal-8S. Additional treatment of endothelial cells with tumour necrosis factor prior to the dynamic shear stress assay entailed an almost 100-fold enhanced adhesion of myeloma cells without addition of Gal-8 variants and a further 1.5-1.7-fold enhancement by addition of Gal-8 variants. We also found that elevated expression of Gal-8 in native multiple myeloma cells is an adverse prognostic factor for overall and event-free survival using patients' gene expression profile data of the total therapy 2 and 3 myeloma studies. Also, elevated concentrations of Gal-8 were detected (45%, 19/42 patients) in sera of multiple myeloma patients compared to those of healthy, age-matched donors. Both experimental and clinical data strongly point to the significance of Gal-8 for multiple myeloma development.
Clinical Cooperation Unit Applied Tumor Immunity, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany.
Myriam
M
Friedel
Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, 80539 München, Germany.
Sabine
S
André
Medizinische Klinik V, Universitätsklinikum Heidelberg und Nationales Centrum für Tumorerkrankungen Heidelberg, 69120 Heidelberg, Germany.
Hartmut
H
Goldschmidt
Institut für Physiologische Chemie, Tierärztliche Fakultät, Ludwig-Maximilians-Universität München, 80539 München, Germany.
Hans-Joachim
HJ
Gabius
Clinical Cooperation Unit Applied Tumor Immunity, Deutsches Krebsforschungszentrum, 69120 Heidelberg, Germany r.s-albiez@dkfz.de.
Reinhard
R
Schwartz-Albiez
D002448:Cell Adhesion; D002478:Cells, Cultured; D004730:Endothelium, Vascular / Q000378:metabolism*; D037161:Galectins / Q000378:metabolism*; D006801:Humans; D009101:Multiple Myeloma / Q000175:diagnosis / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
D037161:Galectins; C091991:LGALS8 protein, human; D011994:Recombinant Proteins
galectin-8; homing; multiple myeloma; shear stress; vascular endothelial cells