| First Author | García-Bernal D | Year | 2013 |
| Journal | J Pathol | Volume | 229 |
| Issue | 1 | Pages | 36-48 |
| PubMed ID | 22711564 | Mgi Jnum | J:190362 |
| Mgi Id | MGI:5448636 | Doi | 10.1002/path.4066 |
| Citation | Garcia-Bernal D, et al. (2013) Sphingosine-1-phosphate activates chemokine-promoted myeloma cell adhesion and migration involving alpha4beta1 integrin function. J Pathol 229(1):36-48 |
| abstractText | Myeloma cell adhesion dependent on alpha4beta1 integrin is crucial for the progression of multiple myeloma (MM). The alpha4beta1-dependent myeloma cell adhesion is up-regulated by the chemokine CXCL12, and pharmacological blockade of the CXCL12 receptor CXCR4 leads to defective myeloma cell homing to bone marrow (BM). Sphingosine-1-phosphate (S1P) regulates immune cell trafficking upon binding to G-protein-coupled receptors. Here we show that myeloma cells express S1P1, a receptor for S1P. We found that S1P up-regulated the alpha4beta1-mediated myeloma cell adhesion and transendothelial migration stimulated by CXCL12. S1P promoted generation of high-affinity alpha4beta1 that efficiently bound the alpha4beta1 ligand VCAM-1, a finding that was associated with S1P-triggered increase in talin-beta1 integrin association. Furthermore, S1P cooperated with CXCL12 for enhancement of alpha4beta1-dependent adhesion strengthening and spreading. CXCL12 and S1P activated the DOCK2-Rac1 pathway, which was required for stimulation of myeloma cell adhesion involving alpha4beta1. Moreover, in vivo analyses indicated that S1P contributes to optimizing the interactions of MM cells with the BM microvasculture and for their lodging inside the bone marrow. The regulation of alpha4beta1-dependent adhesion and migration of myeloma cells by CXCL12-S1P combined activities might have important consequences for myeloma disease progression. Copyright (c) 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd. |
