title: Invasion-associated MMP-2 and MMP-9 are up-regulated intracellularly in concert with apoptosis linked to melanoma cell detachment.
abstract: Matrix metalloproteinases, like MMP-2 and MMP-9 gelatinases, show multiple functions as extracellular/cell-surface enzymes, and are broadly recognised for their matrix-degrading ability and involvement in cell motility. Given that adherent cells have reduced attachment during migration and also detach from their substratum during apoptosis, we now investigated whether extracellular matrix-bound gelatinases and intracellular MMP-2 and MMP-9 are modified with progression of death-inducing stimuli. This report shows that melanoma cells undergoing death in response to 2-acetyl furanonaphtoquinone (FNQ) as evidenced by greater Annexin V binding, increased cytosolic expression of pro-MMP-2 and intracellular activation of particulate MMP-9. These changes were associated with early activation of a substrate-attached 40 kDa gelatinase reciprocal with changes in extracellular matrix-bound activated MMP-2. A subsequent activation of secreted MMP-9 and induction of apoptosis-associated fragmentation of poly ADP-Ribose polymerase (PARP) correlated with cell detachment. Our data suggests that intracellularly activated gelatinases may cleave survival-associated substrates other than gelatin that share the Gly-Leu/Iso-Pro like collagen-binding acetylcholinesterase, thereby linking them to apoptosis associated with cell detachment.
authors.affiliation: Laboratory of Tumor Cell Biology, Centre for Microbiology and Cell Biology, IVIC, Apartado 21827, Caracas, 1020 A, Venezuela. mrieber@ivic.ve
authors.forename: Ana Maria Mendes
authors.initials: AM
authors.lastname: Pereira
authors.forename: Mary
authors.initials: M
authors.lastname: Strasberg-Rieber
authors.forename: Manuel
authors.initials: M
authors.lastname: Rieber
mesh_terms: D000818:Animals; D017304:Annexin A5 / Q000378:metabolism; D017209:Apoptosis; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000201:enzymology; D004789:Enzyme Activation; D005109:Extracellular Matrix / Q000187:drug effects / Q000201:enzymology; D006801:Humans; D020778:Matrix Metalloproteinase 2 / Q000032:analysis / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000032:analysis / Q000378:metabolism*; D008545:Melanoma / Q000201:enzymology* / Q000473:pathology; D051379:Mice; D009285:Naphthoquinones / Q000494:pharmacology; D009361:Neoplasm Invasiveness; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012878:Skin Neoplasms / Q000201:enzymology* / Q000473:pathology; D015854:Up-Regulation; D014867:Water / Q000494:pharmacology
chemical_list: D017304:Annexin A5; D009285:Naphthoquinones; D019253:Proto-Oncogene Proteins c-bcl-2; D014867:Water; D011065:Poly(ADP-ribose) Polymerases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9