Findings from University Hospital Broaden Understanding of Leukemia Gene Therapy (Overexpression of progelatinase B/proMMP-9 affects migration regulatory pathways and impairs chronic lymphocytic leukemia cell homing to bone marrow and spleen)
By a News Reporter-Staff News Editor at Cancer Gene Therapy Week -- Investigators publish new report on Biotechnology. According to news reporting from Madrid, Spain, by NewsRx journalists, research stated, "This study addresses the role of (pro) MMP-9 overexpression in CLL cell migration. We have used primary CLL cells and CLL-derived MEC-1 cells transfected with empty (mock cells) or proMMP-9-encoding (MMP-9 cells) lentiviral vectors."
The news correspondents obtained a quote from the research from University Hospital, "The constitutive (pro) MMP-9 expression in mock cells and primary CLL cells was similar, whereas in MMP-9 cells, expression resembled that of CLL cells incubated with proMMP-9. In xenograft models, in NOD/SCID mice, MMP-9-MEC-1 transfectants showed significantly reduced homing to bone marrow and spleen compared with mock cells. Likewise, incubation of primary CLL cells with proMMP-9, before injection into mice, inhibited their homing to these organs. This inhibition was specific, dose-dependent, and observed in all CLL tested, independently of prognostic markers or disease stage. Additionally, the MMP-9 catalytic activity was only partially involved, as the inactive mutant proMMP-9MutE had a partial effect. MMP-9 cells also showed impaired migration in vitro, which was reverted by reducing (pro) MMP-9 expression with siRNAs. CLL migration thus requires optimal pro) MMP-9 expression levels, below or above which migration is hampered. Biochemical analysis of the (pro) MMP-9 effect indicated that MMP-9 cells or primary CLL cells incubated with proMMP-9 had reduced activation of migration regulatory molecules, including RhoAGTPase, Akt, ERK, and FAK. In contrast, p190RhoGAP (RhoA inhibitor) and PTEN (Akt/ERK/FAK inhibitor) were up-regulated in MMP-9 cells. Reduction of (pro) MMP-9 expression by siRNAs restored RhoA activity and diminished PTEN levels. Our results reveal a novel function for (pro) MMP-9 in modulating signaling pathways leading to CLL cell arrest."
According to the news reporters, the research concluded: "Therefore, local high (pro) MMP-9 expression may contribute to malignant cell retention in lymphoid organs and disease progression."
For more information on this research see: Overexpression of progelatinase B/proMMP-9 affects migration regulatory pathways and impairs chronic lymphocytic leukemia cell homing to bone marrow and spleen. Journal of Leukocyte Biology, 2014;96(2):185-199. Journal of Leukocyte Biology can be contacted at: Federation Amer Soc Exp Biol, 9650 Rockville Pike, Bethesda, MD 20814-3998, USA (see also Biotechnology).
Our news journalists report that additional information may be obtained by contacting E. Bailon, Puerta Hierro University Hospital, Dept. of Hematol, Madrid, Spain. Additional authors for this research include E. Ugarte-Berzal, I. Amigo-Jimenez, P. Van den Steen, G. Opdenakker, J.A. Garcia-Marco and A. Garcia-Pardo.
Keywords for this news article include: Madrid, Spain, Europe, Biotechnology, Bone Marrow, Bone Research, Chronic Lymphocytic Leukemia, Hematology, Hemic and Immune Systems, Leukemia Gene Therapy, Oncology, Spleen
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