RRML - The influence of bone marrow stromal cells on matrix metaloproteinases expression in myeloma cell line L 363

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Nr. 19(4)/2011

The influence of bone marrow stromal cells on matrix metaloproteinases expression in myeloma cell line L 363

Dragos Peptanariu, Dietmar Pfeifer, Mihaela Zlei, Lucian Negura, Tudor Petreus , Dagmar Wider, Monika Engelhardt, Eugen Carasevici

Abstract:

Multiple myeloma (MM) involves slow proliferation of malignant plasma cells and is associated with high serum levels of monoclonal antibodies, increased angiogenesis and osteolysis. The interaction of plasma cells with the bone marrow microenvironment represents a key factor in the development of osteolytic lesions. Matrix metalloproteinases (MMPs) are implicated in tumor growth and invasion, angiogenesis and bone remodeling in many cancers including MM. To assess the influence of the bone marrow microenvironment upon gene expression levels of MMPs from malignant plasma cells, we have developed an in vitro experiment involving co-culture of bone marrow stromal cells (BMSCs) with the L363 myeloma cell line. Following co-culture, microarray analysis was used to compare the expression of all 24 human MMP genes known. Our data revealed no significant change in the expression of MMP-2 in non-adherent L363 cells exposed to interaction and possibly elevated results for MMP-2 gene in the adherent population. Although our microarray data shows a 5.82 fold increase for this gene in the adherent L363 group, it is possible to attribute this to contaminating stroma because MMP-2 is known to be expressed by both BMSCs and MM cells and the purity we have achieved for L363 cells after separation from BMSCs was in the range of 90-95%. For the other MMP genes, both from adherent and non-adherent populations, our results indicate that the BMSC influence on L363 is not significant, this most likely due to the fact that L363 is a leukemic MM cell line and less dependent on stroma as opposed to other MM cell lines or primary MM samples.

Keywords: multiple myeloma,bone marrow stromal cells,matrix metalloproteinases,microarray,gene expression,co-culture.

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Peptanariu D, Pfeifer D, Zlei M, Negura L, T, Wider D, et al. The influence of bone marrow stromal cells on matrix metaloproteinases expression in myeloma cell line L 363. Rev Romana Med Lab. 2011;19(4):359-66