AI Article Synopsis
- Researchers found that MMP-9, when overexpressed, hinders the movement of chronic lymphocytic leukemia (CLL) cells, leading to studies on a mutant form of MMP-9 that doesn't break down proteins (MMP-9MutE).
- In mouse models, these MMP-9MutE cells showed reduced ability to migrate to key areas like the spleen and bone marrow compared to control cells.
- The study identified changes in cellular signaling pathways; MMP-9MutE cells had higher levels of PTEN and lower p-ERK, indicating that non-proteolytic functions of MMP-9 are important in CLL cell migration and may affect disease progression.
Article Abstract
We previously showed that MMP-9 overexpression impairs migration of primary CLL cells and MEC-1 cells transfected with MMP-9. To determine the contribution of non-proteolytic activities to this effect we generated MEC-1 transfectants stably expressing catalytically inactive MMP-9MutE (MMP-9MutE-cells). In xenograft models in mice, MMP-9MutE-cells showed impaired homing to spleen and bone marrow, compared to cells transfected with empty vector (Mock-cells). In vitro transendothelial and random migration of MMP-9MutE-cells were also reduced. Biochemical analyses indicated that RhoAGTPase and p-Akt were not downregulated by MMP-9MutE, at difference with MMP-9. However, MMP-9MutE-cells or primary cells incubated with MMP-9MutE had significantly reduced p-ERK and increased PTEN, accounting for the impaired migration. Our results emphasize the role of non-proteolytic MMP-9 functions contributing to CLL progression.
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| http://dx.doi.org/10.1016/j.bbrc.2017.10.129 | DOI Listing |
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