CXCR3-binding chemokines in multiple myeloma.
The CXC chemokines I-TAC, Mig and IP10 and their receptor CXCR3 are associated with advanced-stage tumor and contribute to tumor progression, invasion and metastasis. The current study was designed to determine the expression of CXCR3 on four multiple myeloma (MM) cell lines and bone marrow plasma cells from 20 MM patients. Cell functions related to progression, such as tyrosine-kinase phosphorylation, proliferation, chemotaxis and matrix metalloproteinase-2 (MMP-2), and MMP-9 secretion were also investigated following the CXCR3/chemokine interaction. fluorescence activated cell sorting analysis revealed that three cell lines (75%) and 18 patients (90%) express the CXCR3 molecule. We demonstrated both in cell lines and fresh plasma cells that I-TAC, Mig and IP10 are able to induce tyrosine-kinase phosphorylation and chemotaxis, but not proliferation, and to increase the MMP-2 and MMP-9 gelatinolytic activity in the cell conditioned medium. Data suggest that CXCR3/chemokine loop may be important for progression of MM in terms of intramedullary and extramedullary dissemination.
Pellegrino
Antonio
A
Department of Biomedical Sciences and Human Oncology, Section of Internal Medicine and Clinical Oncology, University of Bari, Policlinico, Piazza Giulio Cesare 11, Bari I-70124, Italy.
Antonaci
Francesco
F
Russo
Francesca
F
Merchionne
Francesca
F
Ribatti
Domenico
D
Vacca
Angelo
A
Dammacco
Franco
F
D001854:Bone Marrow Cells / Q000378:metabolism / Q000473:pathology; D002455:Cell Division; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC / Q000378:metabolism; D002633:Chemotaxis / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D009101:Multiple Myeloma / Q000378:metabolism* / Q000473:pathology; D010766:Phosphorylation; D010950:Plasma Cells / Q000378:metabolism / Q000473:pathology; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine / Q000378:metabolism*; D014407:Tumor Cells, Cultured
C515202:CXCL11 protein, human; C080810:CXCL9 protein, human; C515187:CXCR3 protein, human; D054357:Chemokine CXCL10; D054371:Chemokine CXCL11; D054370:Chemokine CXCL9; D019743:Chemokines, CXC; D036341:Intercellular Signaling Peptides and Proteins; D054367:Receptors, CXCR3; D019707:Receptors, Chemokine; D011505:Protein-Tyrosine Kinases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9