eISSN: 1896-9151
ISSN: 1734-1922
Archives of Medical Science
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vol. 5

SDF1/CXCR4 signalling promotes mobility of myeloma cells by activation and redistribution of cell surface adhesion molecules

Fu Jinxiang
Zhang Xiaohui
Zhang Yong
Zhang Jianhua
Chen Ping
Li Jun
Sun Yu

Arch Med Sci 2009; 5, 2: 141-148
Online publish date: 2009/07/23
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Introduction: The aim of the study was to investigate the effects of SDF-1a on multiple myeloma (MM) cell migration, adhesion and their corresponding signalling pathways.
Material and methods: We studied the relationship between expression and distribution of the surface adhesion molecules and the ability of MM cells to migrate or adhere to stromal cells with or without SDF-1a in vitro. The effects of activation of phosphatidylinositol 3-kinase (PI3 kinase) in migration of MM cells was also investigated.
Results: Flow cytometry analysis showed that MM cells expressed adhesion molecules such as CD29, CD44, CD49d and CD49e. Our results indicated that the SDF-1/CXCR-4 signalling promotes MM cells to adhere to marrow stromal cells in vitro. The migration of MM cells to stromal cells was enhanced in the presence of SDF-1a in a dose-dependent manner, which was inhibited by either pre-incubation of the MM cells with the G protein inhibitor PTX or the PI3 kinase inhibitor wortmannin. Polarization of adhesion molecules was a marked characteristic observed by confocal laser scanning microscopy (CLSM), which might contribute to the cells’ migration and adhesion to stromal cells. Meanwhile, we demonstrated that PI3 kinase played a role in the signalling pathway leading to Gia activation triggered by CXCL12 in MM cells. The effects of SDF-1/CXCR-4 signalling in MM cells’ polarization and motility might be mediated by Gia, which was required to activate PI3 kinase.
Conclusions: Taken together, it is highlighted that SDF-1/CXCR4 is a critical regulator of MM migration, providing the framework for the inhibitors of this pathway to be used in future clinical trials to abrogate MM trafficking.

multiple myeloma, SDF-1/CXCR4, migration, adhesion molecule, polarization

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