Matrix metalloproteinase regulation of sphingosine-1-phosphate-induced angiogenic properties of bone marrow stromal cells

Membrane-Type 1 Matrix Metalloproteinase Stimulates Cell Migration through Epidermal Growth Factor Receptor Transactivation

“…Because MT1-MMP induces EGFR transactivation in cells stimulated with S1P, we next determined whether or not this stimulatory effect of MT1-MMP translates into an increase in COS-7 cell migration. As we previously reported (45), S1P induced a slight increase in basal cell migration (1.5 F 0.1-fold, P V 0.05), which was further augmented by MT1-MMP overexpression (2.6 F 0.1-fold, P V 0.05; Fig. 3D).…”

“…This cell type has been used in number of studies to determine the signaling mechanisms involved in GPCR-mediated transactivation of EGFR (32,(40)(41)(42)(43)(44). These cells contain detectable amounts of the S1P receptor S1P 1 (45), but no detectable MT1-MMP, and thus constitute an interesting and appropriate cell model to study the mechanisms involved in S1P-stimulated MT1-MMP -dependent EGFR transactivation. MT1-MMP, along with an epitope-tagged EGFR construct (FLAG-EGFR), was overexpressed in COS-7 cells, and following stimulation with S1P, the FLAG-EGFR was immunoprecipitated to monitor its phosphotyrosine content.…”

Epigallocatechin Gallate Targeting of Membrane Type 1 Matrix Metalloproteinase-mediated Src and Janus Kinase/Signal Transducers and Activators of Transcription 3 Signaling Inhibits Transcription of Colony-stimulating Factors 2 and 3 in Mesenchymal Stromal Cells

“…1 ated signaling in concanavalin A (ConA)-activated MSCs that could regulate the expression of the inflammation biomarker cyclooxygenase-2 (12). Interestingly, aside from its canonical role in extracellular matrix proteolysis, MT1-MMP is also involved in transducing crucial intracellular signaling that may control several processes related to MSC mobilization and cell survival (13)(14)(15). In this study, we demonstrate that, as a consequence of ConA activation, sequential Src kinase and JAK/ STAT3 signaling is required to up-regulate CSF-2 and CSF-3 transcription and that this necessitates the contribution of MT1-MMP transduction through the crucial involvement of a phosphorylatable Tyr 573 residue located within its 20-amino acid cytoplasmic domain.…”

Targeting sphingosine-1-phosphate for cancer therapy

“…Sphingosine-1-phosphate stimulates DNA synthesis and chemotactic motility of human venous ECs (HUVECs), whereas inducing differentiation of multicellular structures, all of which is suggestive of S1P's role in early blood-vessel formation (Lee et al, 1999;Liu et al, 2000;Argraves et al, 2004). Also, S1P promotes the migration of bone marrow-derived EC precursors to neovascularisation sites (Annabi et al, 2003). Cells that overexpress S1P 1 are resistant to the antiangiogenic agents thalidomide and Neovastat (Annabi et al, 2003).…”

“…Also, S1P promotes the migration of bone marrow-derived EC precursors to neovascularisation sites (Annabi et al, 2003). Cells that overexpress S1P 1 are resistant to the antiangiogenic agents thalidomide and Neovastat (Annabi et al, 2003). In addition, it has been demonstrated that substantial crosstalk exists between S1P and other proangiogenic growth factors such as VEGF, EGF, PDGF, bFGF and IL-8.…”