Journal
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Volume 495, Issue 1, Pages 124-130Publisher
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.bbrc.2017.10.129
Keywords
CLL; Non-proteolytic MMP-9; Signaling pathways; Cell migration; Homing
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Funding
- Ministry of Economy and Competitivity (Spain) [SAF2015-69180R]
- Red Tematica de Investigacion Cooperativa en Cancer from the Ministry of Economy and Competitivity (Spain) [RD12/0036/0061]
- Comunidad de Madrid/European Union [S2010/BMD-2314]
- Concerted Research Actions [GOA 2013/015, C1/2017, C16/17/010]
- Foundation for Scientific Research of Flanders (FWO-Vlaanderen) [G0A7516N, G0A5716N]
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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. (C) 2017 Elsevier Inc. All rights reserved.
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