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Invasion-associated MMP-2 and MMP-9 are Up-regulated Intracellularly in Concert with Apoptosis Linked to Melanoma Cell Detachment

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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.

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Abbreviations

AchE:

acetylcholinesterase

ECM-bound:

extracellular matrix-bound

FNQ:

2-acetyl furanonaphthoquinone

MMP-2:

matrix metalloprotease 2 or gelatinase A

MMP-9:

matrix metalloprotease 9 or gelatinase B

PARP:

poly ADP-Ribose polymerase

References

  1. G Glinsky V Glinsky A Ivanova C Hueser (1997) ArticleTitleApoptosis and metastasis: Increased apoptosis resistance of metastatic cancer cells is associated with the profound deficiency of apoptosis execution mechanisms Cancer Lett 115 IssueID2 185–93 Occurrence Handle10.1016/S0304-3835(97)04738-1 Occurrence Handle9149123

    Article  PubMed  Google Scholar 

  2. C Wong A Lee L Shientag et al. (2001) ArticleTitleApoptosis: An early event in metastatic inefficiency Cancer Res. 61 IssueID1 333–8 Occurrence Handle11196183

    PubMed  Google Scholar 

  3. J Fata A Ho K Leco et al. (2000) ArticleTitleCellular turnover and extracellular matrix remodeling in female reproductive tissues: Functions of metalloproteinases and their inhibitors Cell Mol Life Sci 57 IssueID1 77–95 Occurrence Handle10.1007/s000180050500 Occurrence Handle10949582

    Article  PubMed  Google Scholar 

  4. N Ortega D Behonick D Stickens Z Werb (2003) ArticleTitleHow proteases regulate bone morphogenesis Ann NY Acad Sci 995 109–16 Occurrence Handle12814943

    PubMed  Google Scholar 

  5. A Chambers L Matrisian (1997) ArticleTitleChanging views of the role of matrix metalloproteinases in metastasis J Natl Cancer Inst 89 IssueID17 1260–70 Occurrence Handle10.1093/jnci/89.17.1260 Occurrence Handle9293916

    Article  PubMed  Google Scholar 

  6. C Alexander E Howard M Bissell Z Werb (1996) ArticleTitleRescue of mammary epithelial cell apoptosis and entactin degradation by a tissue inhibitor of metalloproteinases-1 transgene J Cell Biol 135 1669–77 Occurrence Handle10.1083/jcb.135.6.1669 Occurrence Handle8978831

    Article  PubMed  Google Scholar 

  7. N Boudreau C Sympson Z Werb M Bissell (1995) ArticleTitleSuppression of ICE and apoptosis in mammary epithelial cells by extracellular matrix Science 267 IssueID5199 891–3 Occurrence Handle7531366

    PubMed  Google Scholar 

  8. S Frisch R Screaton (2001) ArticleTitleAnoikis mechanisms Curr Opin Cell Biol 13 IssueID5 555–62 Occurrence Handle10.1016/S0955-0674(00)00251-9 Occurrence Handle11544023

    Article  PubMed  Google Scholar 

  9. W Powell B Fingleton C Wilson et al. (1999) ArticleTitleThe metalloproteinase matrilysin proteolytically generates active soluble Fas ligand and potentiates epithelial resistant cell apoptosis Curr Biol 9 IssueID24 1441–7 Occurrence Handle10.1016/S0960-9822(00)80113-X Occurrence Handle10607586

    Article  PubMed  Google Scholar 

  10. A Banerji J Chakrabarti A Mitra A Chatterjee (2004) ArticleTitleEffect of curcumin on gelatinase A (MMP-2) activity in B16F10 melanoma cells Cancer Lett 211 IssueID2 235–42 Occurrence Handle10.1016/j.canlet.2004.02.007 Occurrence Handle15219947

    Article  PubMed  Google Scholar 

  11. U Hofmann J Westphal G Muijen ParticleVan D Ruiter (2000) ArticleTitleMatrix metalloproteinases in human melanoma J Invest Dermatol 115 IssueID3 337–44 Occurrence Handle10.1046/j.1523-1747.2000.00068.x Occurrence Handle10951266

    Article  PubMed  Google Scholar 

  12. J Ray W Stetler-Stevenson (1995) ArticleTitleGelatinase A activity directly modulates melanoma cell adhesion and spreading EMBO J 14 IssueID5 908–17 Occurrence Handle7534227

    PubMed  Google Scholar 

  13. J MacDougall M Bani Y Lin et al. (1995) ArticleTitleThe 92-kDa gelatinase B is expressed by advanced stage melanoma cells: Suppression by somatic cell hybridization with early stage melanoma cells Cancer Res 55 IssueID18 4174–81 Occurrence Handle7664294

    PubMed  Google Scholar 

  14. M Strasberg-Rieber D.R Welch M Rieber (2001) ArticleTitleSuppression of C8161 melanoma metastatic ability by chromosome 6 induces differentiation-associated tyrosinase and decreases proliferation on adhesion-restrictive substrates mediated by overexpression of p21WAF1 and down-regulation of bcl-2 and cyclin D3 Biochem Biophys Res Commun 281 159–65 Occurrence Handle10.1006/bbrc.2001.4330 Occurrence Handle11178974

    Article  PubMed  Google Scholar 

  15. C Vaillant C Meissirel M Mutin et al. (2003) ArticleTitleMMP-9 deficiency affects axonal outgrowth, migration, and apoptosis in the developing cerebellum Mol Cell Neurosci 24 IssueID2 395–408 Occurrence Handle10.1016/S1044-7431(03)00196-9 Occurrence Handle14572461

    Article  PubMed  Google Scholar 

  16. L Solorzano M Strasberg Rieber M Ad Rieber (2000) ArticleTitleLower cyclin H and cyclin-dependent kinase-activating kinase activity in cell cycle arrest induced by lack of adhesión to substratum Cancer Res 60 7114–8 Occurrence Handle11156419

    PubMed  Google Scholar 

  17. M Strasberg-Rieber U Zangemeister-Wittke M Rieber (2001) ArticleTitlep53-Independent induction of apoptosis in human melanoma cells by a bcl-2/bcl-xL bispecific antisense oligonucleotide Clin Cancer Res 7 IssueID5 1446–51 Occurrence Handle11350916

    PubMed  Google Scholar 

  18. M Rieber M Strasberg-Rieber (2003) ArticleTitleN-acetyl cysteine enhances UV-mediated caspase 3 activation, fragmentation of E2F-4 and apoptosis in human C8161 melanoma: inhibition by ectopic bcl-2 expression Biochem Pharmacol 65 1593–1601 Occurrence Handle10.1016/S0006-2952(03)00147-3 Occurrence Handle12754095

    Article  PubMed  Google Scholar 

  19. K Hirai J Koyama J Pan et al. (1999) ArticleTitleFuranonaphthoquinone analogs possessing preferential antitumor activity compared to normal cells Cancer Detect Prev 23 IssueID6 539–50 Occurrence Handle10.1046/j.1525-1500.1999.99052.x Occurrence Handle10571665

    Article  PubMed  Google Scholar 

  20. M Rieber JD Medina M Strasberg-Rieber (2002) ArticleTitleRelationship of Mcl-1 isoforms, ratio p21WAF1/cyclin A and Jun Kinase phosphorylation to apoptosis in human breast carcinomas Biochem Biophys Res Comm 297 943–9 Occurrence Handle10.1016/S0006-291X(02)02312-4 Occurrence Handle12359245

    Article  PubMed  Google Scholar 

  21. G Fiskum S Craig G Decker A Lehninger (1980) ArticleTitleThe cytoskeleton of digitonin-treated rat hepatocytes Proc Natl Acad Sci USA 77 IssueID6 3430–4 Occurrence Handle6997878

    PubMed  Google Scholar 

  22. M Strasberg-Rieber D Welch M Miele M Rieber (1996) ArticleTitlep53-independent increase in p21WAF1 and reciprocal down-regulation of cyclin A and proliferating cell nuclear antigen in bromodeoxyuridine-mediated growth arrest of human melanoma cells Cell Growth Differ 7 197–202 Occurrence Handle8822203

    PubMed  Google Scholar 

  23. P Daniel I Sturm S Ritschel et al. (1999) ArticleTitleDetection of genomic DNA fragmentation during apoptosis (DNA ladder) and the simultaneous isolation of RNA from low cell numbers Anal Biochem 266 IssueID1 110–5 Occurrence Handle10.1006/abio.1998.2929 Occurrence Handle9887219

    Article  PubMed  Google Scholar 

  24. Y Lazebnik S Kaufmann S Desnoyers et al. (1994) ArticleTitleCleavage of poly(ADP-ribose) polymerase by a proteinase with properties like ICE Nature 371 IssueID6495 346–7 Occurrence Handle10.1038/371346a0 Occurrence Handle8090205

    Article  PubMed  Google Scholar 

  25. VA Fadok DL Bratton SC Frasch et al. (1998) ArticleTitleThe role of phosphatidylserine in recognition of apoptotic cells by phagocytes Cell Death Differ 5 557–563 Occurrence Handle10.1038/sj.cdd.4400404

    Article  Google Scholar 

  26. A Simm G Bertsch H Frank et al. (1997) ArticleTitleCell death of AKR-2B fibroblasts after serum removal: A process between apoptosis and necrosis J Cell Sci 110 819–28 Occurrence Handle9133669

    PubMed  Google Scholar 

  27. M Egeblad M Jaattela (2000) ArticleTitleCell death induced by TNF or serum starvation is independent of ErbB receptor signaling in MCF-7 breast carcinoma cells Int J Cancer 86 617–25 Occurrence Handle10.1002/(SICI)1097-0215(20000601)86:5<617::AID-IJC3>3.0.CO;2-Z Occurrence Handle10797281

    Article  PubMed  Google Scholar 

  28. C Jackson M Nguyen (1997) ArticleTitleHuman microvascular endothelial cells differ from macrovascular endothelial cells in their expression of matrix metalloproteinases Int J Biochem Cell Biol 29 IssueID10 1167–77 Occurrence Handle10.1016/S1357-2725(97)00061-7 Occurrence Handle9438380

    Article  PubMed  Google Scholar 

  29. H Nagase (1998) ArticleTitleCell surface activation of progelatinase A (proMMP-2) and cell migration Cell Res 8 IssueID3 179–86 Occurrence Handle9791731

    PubMed  Google Scholar 

  30. U Bergmann A Tuuttila W Stetler-Stevenson K Tryggvason (1995) ArticleTitleAutolytic activation of recombinant human 72 kilodalton type IV collagenase Biochemistry 34 IssueID9 2819–25 Occurrence Handle10.1021/bi00009a011 Occurrence Handle7893694

    Article  PubMed  Google Scholar 

  31. J Pan K Hirai E Simamura et al. (1997) ArticleTitleMitochondrial damage by a new antitumor agent furanonaphthoquinone derivative in human cervical cancer cells J Electron Microsc 46 IssueID2 181–7

    Google Scholar 

  32. LJ Jones VL Singer (2001) ArticleTitleFluorescence microplate-based assay for tumor necrosis factor activity using SYTOX Green stain Anal Biochem 293 8–15 Occurrence Handle10.1006/abio.2001.5116 Occurrence Handle11373072

    Article  PubMed  Google Scholar 

  33. L McCawley L Matrisian (2001) ArticleTitleMatrix metalloproteinase: They’re not just for matrix anymore! Curr Opin Cell Biol. 13 534–40 Occurrence Handle10.1016/S0955-0674(00)00248-9 Occurrence Handle11544020

    Article  PubMed  Google Scholar 

  34. J Sancéau S Truchet B Bauvois (2003) ArticleTitleMatrix metalloproteinase-9 silencing by RNA interference triggers the migratory-adhesive switch in Ewing’s sarcoma cells J Biol Chem 278 36537–46 Occurrence Handle10.1074/jbc.M304300200 Occurrence Handle12847101

    Article  PubMed  Google Scholar 

  35. M Egeblad Z Werb (2002) ArticleTitleNew functions for the matrix metalloproteinases in cancer progression Nat Rev Cancer 2 IssueID3 161–74 Occurrence Handle10.1038/nrc745 Occurrence Handle11990853

    Article  PubMed  Google Scholar 

  36. S Chintala X Zhang J Austin M Fini (2002) ArticleTitleDeficiency in matrix metalloproteinase gelatinase B (MMP-9) protects against retinal ganglion cell death after optic nerve ligation J Biol Chem 277 IssueID49 47461–8 Occurrence Handle10.1074/jbc.M204824200 Occurrence Handle12354772

    Article  PubMed  Google Scholar 

  37. M Nguyen J Arkell C Jackson (1998) ArticleTitleActive and tissue inhibitor of matrix metalloproteinase-free gelatinase B accumulates within human microvascular endothelial vesicles J Biol Chem 273 5400–4 Occurrence Handle10.1074/jbc.273.9.5400 Occurrence Handle9479001

    Article  PubMed  Google Scholar 

  38. G Gazzanelli F Luchetti S Burattini et al. (2000) ArticleTitleMatrix metalloproteinases expression in HL-60 promyelocytic leukemia cells during apoptosis Apoptosis 5 IssueID2 165–72 Occurrence Handle10.1023/A:1009688831531 Occurrence Handle11232244

    Article  PubMed  Google Scholar 

  39. J Kwan C Schulze W Wang (2004) ArticleTitleMatrix metalloproteinase-2 (MMP-2) is present in the nucleus of cardiac myocytes and is capable of cleaving poly (ADP-ribose) polymerase (PARP) in vitro FASEB J 18 IssueID6 690–2 Occurrence Handle14766804

    PubMed  Google Scholar 

  40. G Johnson S Moore (1999) ArticleTitleThe adhesion function on acetylcholinesterase is located at the peripheral anionic site Biochem Biophys Res Commun 258 IssueID3 758–62 Occurrence Handle10.1006/bbrc.1999.0705 Occurrence Handle10329459

    Article  PubMed  Google Scholar 

  41. K Sharma C Koenigsberger S Brimijoin J Bigbee (2001) ArticleTitleDirect evidence for an adhesive function in the noncholinergic role of acetylcholinesterase in neurite outgrowth J Neurosci Res 63 165–75 Occurrence Handle10.1002/1097-4547(20010115)63:2<165::AID-JNR1008>3.0.CO;2-O Occurrence Handle11169626

    Article  PubMed  Google Scholar 

  42. M Sailer M Oppitz U Drews (2000) ArticleTitleInduction of cellular contractions in the human melanoma cell line SK-Mel 28 after muscarinic cholinergic stimulation Anat Embryol (Berl) 201 27–37

    Google Scholar 

  43. D Hand D Dias LW Haynes (2000) ArticleTitleStabilization of collagen-tailed acetylcholinesterase in muscle cells through extracellular anchorage by transglutaminase-catalyzed cross-linking Mol Cell Biochem J20 65–76 Occurrence Handle10.1023/A:1007068017315

    Article  Google Scholar 

  44. XJ Zhang L Yang Q Zhao et al. (2002) ArticleTitleInduction of acetylcholinesterase expression during apoptosis in various cell types Cell Death Differ 9 790–800 Occurrence Handle10.1038/sj.cdd.4401034 Occurrence Handle12107822

    Article  PubMed  Google Scholar 

  45. SE Park ND Nam Deuk Kim YH Young Hyun Yoo (2004) ArticleTitleAcetylcholinesterase Plays a Pivotal Role in Apoptosome Formation Cancer Res 64 2652–5 Occurrence Handle10.1158/0008-5472.CAN-04-0649 Occurrence Handle15087373

    Article  PubMed  Google Scholar 

  46. S Oliverio A Amendola C Rodolfo et al. (1999) ArticleTitleInhibition of “tissue” transglutaminase increases cell survival by preventing apoptosis J Biol Chem 274 34123–8 Occurrence Handle10.1074/jbc.274.48.34123 Occurrence Handle10567382

    Article  PubMed  Google Scholar 

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Authors and Affiliations

  1. Laboratory of Tumor Cell Biology, Centre for Microbiology and Cell Biology, IVIC, Apartado 21827, Caracas, 1020 A, Venezuela

    Ana Maria Mendes Pereira, Mary Strasberg-Rieber & Manuel Rieber

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  1. Ana Maria Mendes Pereira
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  2. Mary Strasberg-Rieber
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  3. Manuel Rieber
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Correspondence to Manuel Rieber.

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Pereira, A.M.M., Strasberg-Rieber, M. & Rieber, M. Invasion-associated MMP-2 and MMP-9 are Up-regulated Intracellularly in Concert with Apoptosis Linked to Melanoma Cell Detachment. Clin Exp Metastasis 22, 285–295 (2005). https://doi.org/10.1007/s10585-005-8672-8

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  • DOI: https://doi.org/10.1007/s10585-005-8672-8

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