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Opioids and matrix metalloproteinases: the influence of morphine on MMP-9 production and cancer progression

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Abstract

Opioids are widely administered to alleviate pain, including chronic pain in advanced cancer patients. Among opioids, morphine is one of the most clinically effective drugs for the palliative management of severe pain. In the last few decades, there has been a debate around the possible influence of opioids such as morphine on tumour growth and metastasis. Whilst several in vitro and in vivo studies suggest the possible modulatory effects of morphine on tumour cells, little is known about the impact of this analgesic drug on other mediators such as matrix metalloproteinases (MMPs) that play a key role in the control of cancer cell invasion and metastasis. MMP-9 has been considered as one of the principal mediators in regulation of not only the initial steps of cancer but during the invasion and spreading of cancer cells to distant organs. Herein, current studies regarding the direct and indirect effects of morphine on regulation of MMP-9 production are discussed. In addition, drawing from previous in vivo and in vitro studies on morphine action in regulating MMP-9 production, the potential roles of several underlying factors are summarised, including nuclear factor kappa-B and intracellular molecules such as nitric oxide.

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Abbreviations

AC:

Adenylyl cyclase

AP-1:

Activator protein 1

BMM:

Bone marrow-derived macrophages

CREB:

cAMP responsive element binding

cAMP:

Cyclic adenosine monophosphate

cGMP:

Cyclic guanosine monophosphate

cNOS:

Constitutive nitric oxide synthase

DRG:

Dorsal root ganglia

eNOS:

Endothelial nitric oxide synthase

ECM:

Extracellular matrix

GPCR:

G protein-coupled receptor

Gβγ:

G beta-gamma

iNOS:

Inducible nitric oxide synthase

IL-1β:

Interleukin 1 beta

IL-4:

Interleukin 4

IL-6:

Interleukin 6

IκB:

Nuclear factor-κB inhibitor

LPS:

Lipopolysaccharide

MMPs:

Matrix metalloproteinases

MMP-9:

Matrix metalloproteinase 9

NF-κB:

Nuclear factor kappa B

NO:

Nitric oxide

NOS:

Nitric oxide synthase

nNOS:

Neuronal nitric oxide synthase

PKCδ:

Protein kinase C-delta

PKA:

Protein kinase A

PLC:

Phospholipase C

PKC:

Protein kinase C

PI3K:

Phosphoinositide 3-kinase

PKB:

Protein kinase B

PEA3:

Polyoma enhancer activator 3

Sp-1:

Stimulating protein-1

TNFR-6:

Tumour necrosis factor receptor-associated factor 6

TLR:

Toll-like receptor

TIMP-1:

Tissue inhibitor of metalloproteinase 1

TNF-α:

Tumour necrosis factor alpha

References

  • Afsharimani B, Cabot P, Parat MO (2011a) Morphine and tumor growth and metastasis. Cancer Metastasis Rev 30:225–238

    Article  CAS  PubMed  Google Scholar 

  • Afsharimani B, Cabot PJ, Parat MO (2011b) Morphine use in cancer surgery. Front Pharmacol 2:46

    Article  PubMed  PubMed Central  Google Scholar 

  • Afsharimani B, Baran J, Watanabe S, Lindner D, Cabot PJ, Parat MO (2014) Morphine and breast tumor metastasis: the role of matrix-degrading enzymes. Clin Exp Metastasis 31:149–158

    Article  CAS  PubMed  Google Scholar 

  • Azuma Y, Ohura K (2002) Endomorphins 1 and 2 inhibit IL-10 and IL-12 production and innate immune functions, and potentiate NF-kappaB DNA binding in THP-1 differentiated to macrophage-like cells. Scand J Immunol 56:260–269

    Article  CAS  PubMed  Google Scholar 

  • Baeuerle PA, Henkel T (1994) Function and activation of NF-kappa B in the immune system. Annu Rev Immunol 12:141–179

    Article  CAS  PubMed  Google Scholar 

  • Beltran JA, Peek J, Chang SL (2006) Expression and regulation of the mu opioid peptide receptor in TPA-differentiated HL-60 promyelocytic leukemia cells. Int Immunopharmacol 6:1331–1340

    Article  CAS  PubMed  Google Scholar 

  • Bergers G, Brekken R, McMahon G, Vu TH, Itoh T, Tamaki K, Tanzawa K, Thorpe P, Itohara S, Werb Z, Hanahan D (2000) Matrix metalloproteinase-9 triggers the angiogenic switch during carcinogenesis. Nat Cell Biol 2:737–744

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Bilfinger TV, Hartman AR, Liu Y, Magazine HI, Stefano GB (1997) Cryopreserved veins in myocardial revascularization: possible mechanism for their increased failure. Ann Thorac Surg 63:1063–1069

    Article  CAS  PubMed  Google Scholar 

  • Bilfinger TV, Fimiani C, Stefano GB (1998) Morphine's immunoregulatory actions are not shared by fentanyl. Int J Cardiol 64(Suppl 1):S61–S66

    Article  PubMed  Google Scholar 

  • Bimonte S, Barbieri A, Palma G, Arra C (2013) The role of morphine in animal models of human cancer: does morphine promote or inhibit the tumor growth? Biomed Res Int 2013:258141

    PubMed  PubMed Central  Google Scholar 

  • Borner C, Kraus J (2013) Inhibition of NF-kappaB by opioids in T cells. J Immunol 191:4640–4647

    Article  CAS  PubMed  Google Scholar 

  • Borner C, Hollt V, Kraus J (2012) Mechanisms of the inhibition of nuclear factor-kappa B by morphine in neuronal cells. Mol Pharmacol 81:587–597

    Article  CAS  PubMed  Google Scholar 

  • Bove PF, Wesley UV, Greul AK, Hristova M, Dostmann WR, van der Vliet A (2007) Nitric oxide promotes airway epithelial wound repair through enhanced activation of MMP-9. Am J Respir Cell Mol Biol 36:138–146

    Article  CAS  PubMed  Google Scholar 

  • Brunet A, Datta SR, Greenberg ME (2001) Transcription-dependent and -independent control of neuronal survival by the PI3K-Akt signaling pathway. Curr Opin Neurobiol 11:297–305

    Article  CAS  PubMed  Google Scholar 

  • Cadet P, Rasmussen M, Zhu W, Tonnesen E, Mantione KJ, Stefano GB (2004) Endogenous morphinergic signaling and tumor growth. Front Biosci 9:3176–3186

    Article  CAS  PubMed  Google Scholar 

  • Carr DJ, Carpenter GW, Garza HH Jr, France CP, Prakash OM (1995) Chronic & infrequent opioid exposure suppresses IL-2R expression on rhesus monkey peripheral blood mononuclear cells following stimulation with pokeweed mitogen. Int J Neurosci 81:137–148

    Article  CAS  PubMed  Google Scholar 

  • Charbaji N, Rosenthal P, Schafer-Korting M, Kuchler S (2013) Cytoprotective effects of opioids on irradiated oral epithelial cells. Wound Repair Regen 21:883–889

    Article  PubMed  Google Scholar 

  • Chen HH, Wang DL (2004) Nitric oxide inhibits matrix metalloproteinase-2 expression via the induction of activating transcription factor 3 in endothelial cells. Mol Pharmacol 65:1130–1140

    Article  CAS  PubMed  Google Scholar 

  • Chen Y, Mestek A, Liu J, Yu L (1993) Molecular cloning of a rat kappa opioid receptor reveals sequence similarities to the mu and delta opioid receptors. Biochem J 295(Pt 3):625–628

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Colasanti M, Persichini T, Menegazzi M, Mariotto S, Giordano E, Caldarera CM, Sogos V, Lauro GM, Suzuki H (1995) Induction of nitric oxide synthase mRNA expression. Suppression by exogenous nitric oxide. J Biol Chem 270:26731–26733

    Article  CAS  PubMed  Google Scholar 

  • Coussens LM, Werb Z (1996) Matrix metalloproteinases and the development of cancer. Chem Biol 3:895–904

    Article  CAS  PubMed  Google Scholar 

  • Coussens LM, Tinkle CL, Hanahan D, Werb Z (2000) MMP-9 supplied by bone marrow-derived cells contributes to skin carcinogenesis. Cell 103:481–490

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Cox BM, Christie MJ, Devi L, Toll L, Traynor JR (2015) Challenges for opioid receptor nomenclature: IUPHAR Review 9. Br J Pharmacol 172:317–323

    Article  CAS  PubMed  Google Scholar 

  • Dahl KDC, Zeineldin R, Hudson LG (2007) PEA3 is necessary for optimal epidermal growth factor receptor-stimulated matrix metalloproteinase expression and invasion of ovarian tumor cells. Mol Cancer Res 5:413–421

    Article  CAS  Google Scholar 

  • de Launoit Y, Baert JL, Chotteau-Lelievre A, Monte D, Coutte L, Mauen S, Firlej V, Degerny C, Verreman K (2006) The Ets transcription factors of the PEA3 group: transcriptional regulators in metastasis. Biochim Biophys Acta 1766:79–87

    PubMed  Google Scholar 

  • Drouet C, Shakhov AN, Jongeneel CV (1991) Enhancers and transcription factors controlling the inducibility of the tumor necrosis factor-alpha promoter in primary macrophages. J Immunol 147:1694–1700

    CAS  PubMed  Google Scholar 

  • Duffy MJ (2004) The urokinase plasminogen activator system: role in malignancy. Curr Pharm Des 10:39–49

    Article  CAS  PubMed  Google Scholar 

  • Eberhardt W, Beeg T, Beck KF, Walpen S, Gauer S, Bohles H, Pfeilschifter J (2000a) Nitric oxide modulates expression of matrix metalloproteinase-9 in rat mesangial cells. Kidney Int 57:59–69

    Article  CAS  PubMed  Google Scholar 

  • Eberhardt W, Huwiler A, Beck KF, Walpen S, Pfeilschifter J (2000b) Amplification of IL-1 beta-induced matrix metalloproteinase-9 expression by superoxide in rat glomerular mesangial cells is mediated by increased activities of NF-kappa B and activating protein-1 and involves activation of the mitogen-activated protein kinase pathways. J Immunol 165:5788–5797

    Article  CAS  PubMed  Google Scholar 

  • Engbring JA, Kleinman HK (2003) The basement membrane matrix in malignancy. J Pathol 200:465–470

    Article  CAS  PubMed  Google Scholar 

  • Esteve PO, Chicoine E, Robledo O, Aoudjit F, Descoteaux A, Potworowski EF, St-Pierre Y (2002) Protein kinase C-zeta regulates transcription of the matrix metalloproteinase-9 gene induced by IL-1 and TNF-alpha in glioma cells via NF-kappa B. J Biol Chem 277:35150–35155

    Article  CAS  PubMed  Google Scholar 

  • Evans CJ, Keith DE Jr, Morrison H, Magendzo K, Edwards RH (1992) Cloning of a delta opioid receptor by functional expression. Science 258:1952–1955

    Article  CAS  PubMed  Google Scholar 

  • Fimiani C, Arcuri E, Santoni A, Rialas CM, Bilfinger TV, Peter D, Salzet B, Stefano GB (1999) Mu3 opiate receptor expression in lung and lung carcinoma: ligand binding and coupling to nitric oxide release. Cancer Lett 146:45–51

    Article  CAS  PubMed  Google Scholar 

  • Fukuda K, Kato S, Mori K, Nishi M, Takeshima H (1993) Primary structures and expression from cDNAs of rat opioid receptor delta- and mu-subtypes. FEBS Lett 327:311–314

    Article  CAS  PubMed  Google Scholar 

  • Fukuda K, Kato S, Morikawa H, Shoda T, Mori K (1996) Functional coupling of the delta-, mu-, and kappa-opioid receptors to mitogen-activated protein kinase and arachidonate release in Chinese hamster ovary cells. J Neurochem 67:1309–1316

    Article  CAS  PubMed  Google Scholar 

  • Gach K, Szemraj J, Wyrebska A, Janecka A (2011a) The influence of opioids on matrix metalloproteinase-2 and -9 secretion and mRNA levels in MCF-7 breast cancer cell line. Mol Biol Rep 38:1231–1236

    Article  CAS  PubMed  Google Scholar 

  • Gach K, Wyrebska A, Fichna J, Janecka A (2011b) The role of morphine in regulation of cancer cell growth. Naunyn Schmiedeberg's Arch Pharmacol 384:221–230

    Article  CAS  Google Scholar 

  • Gach K, Wyrebska A, Szemraj J, Janecka A (2012) The influence of opioid peptides on matrix metalloproteinase-9 and urokinase plasminogen activator expression in three cancer cell lines. Mol Biol 46:894–899

    Article  CAS  Google Scholar 

  • Gordon GM, Ledee DR, Feuer WJ, Fini ME (2009) Cytokines and signaling pathways regulating matrix metalloproteinase-9 (MMP-9) expression in corneal epithelial cells. J Cell Physiol 221:402–411

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Gurjar MV, DeLeon J, Sharma RV, Bhalla RC (2001) Mechanism of inhibition of matrix metalloproteinase-9 induction by NO in vascular smooth muscle cells. J Appl Physiol (1985) 91:1380–1386

    Article  CAS  Google Scholar 

  • Hamada T, Duarte S, Tsuchihashi S, Busuttil RW, Coito AJ (2009) Inducible nitric oxide synthase deficiency impairs matrix metalloproteinase-9 activity and disrupts leukocyte migration in hepatic ischemia/reperfusion injury. Am J Pathol 174:2265–2277

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100:57–70

    Article  CAS  PubMed  Google Scholar 

  • Handal M, Grung M, Skurtveit S, Ripel A, Morland J (2002) Pharmacokinetic differences of morphine and morphine-glucuronides are reflected in locomotor activity. Pharmacol Biochem Behav 73:883–892

    Article  CAS  PubMed  Google Scholar 

  • Harimaya Y, Koizumi K, Andoh T, Nojima H, Kuraishi Y, Saiki I (2002) Potential ability of morphine to inhibit the adhesion, invasion and metastasis of metastatic colon 26-L5 carcinoma cells. Cancer Lett 187:121–127

    Article  CAS  PubMed  Google Scholar 

  • Henry DJ, Grandy DK, Lester HA, Davidson N, Chavkin C (1995) Kappa-opioid receptors couple to inwardly rectifying potassium channels when coexpressed by Xenopus oocytes. Mol Pharmacol 47:551–557

    CAS  PubMed  Google Scholar 

  • Huang S, Van Arsdall M, Tedjarati S, McCarty M, Wu W, Langley R, Fidler IJ (2002) Contributions of stromal metalloproteinase-9 to angiogenesis and growth of human ovarian carcinoma in mice. J Natl Cancer Inst 94:1134–1142

    Article  CAS  PubMed  Google Scholar 

  • Huang Y, Lu MQ, Li H, Xu C, Yi SH, Chen GH (2006) Occurrence of cGMP/nitric oxide-sensitive store-operated calcium entry in fibroblasts and its effect on matrix metalloproteinase secretion. World J Gastroenterol 12:5483–5489

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hutchinson MR, Zhang YN, Shridhar M, Evans JH, Buchanan MM, Zhao TX, Slivka PF, Coats BD, Rezvani N, Wieseler J, Hughes TS, Landgraf KE, Chan S, Fong S, Phipps S, Falke JJ, Leinwand LA, Maier SF, Yin H, Rice KC, Watkins LR (2010) Evidence that opioids may have toll-like receptor 4 and MD-2 effects. Brain Behav Immun 24:83–95

    Article  CAS  PubMed  Google Scholar 

  • Hutchinson MR, Shavit Y, Grace PM, Rice KC, Maier SF, Watkins LR (2011) Exploring the neuroimmunopharmacology of opioids: an integrative review of mechanisms of central immune signaling and their implications for opioid analgesia. Pharmacol Rev 63:772–810

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Hutchinson MR, Northcutt AL, Hiranita T, Wang X, Lewis SS, Thomas J, van Steeg K, Kopajtic TA, Loram LC, Sfregola C, Galer E, Miles NE, Bland ST, Amat J, Rozeske RR, Maslanik T, Chapman TR, Strand KA, Fleshner M, Bachtell RK, Somogyi AA, Yin H, Katz JL, Rice KC, Maier SF, Watkins LR (2012) Opioid activation of toll-like receptor 4 contributes to drug reinforcement. J Neurosci 32:11187–11200

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Jespersen C, Doller A, Akool el S, Bachmann M, Muller R, Gutwein P, Muhl H, Pfeilschifter J, Eberhardt W (2009) Molecular mechanisms of nitric oxide-dependent inhibition of TPA-induced matrix metalloproteinase-9 (MMP-9) in MCF-7 cells. J Cell Physiol 219:276–287

    Article  CAS  PubMed  Google Scholar 

  • Katsuyama K, Shichiri M, Marumo F, Hirata Y (1998) NO inhibits cytokine-induced iNOS expression and NF-kappa B activation by interfering with phosphorylation and degradation of I kappa B-alpha. Arterioscler Thromb Vasc Biol 18:1796–1802

    Article  CAS  PubMed  Google Scholar 

  • Kessenbrock K, Plaks V, Werb Z (2010) Matrix metalloproteinases: regulators of the tumor microenvironment. Cell 141:52–67

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khabbazi S, Goumon Y, Parat MO (2015) Morphine modulates Interleukin-4-or breast cancer cell-induced pro-metastatic activation of macrophages. Sci Rep 5:11389

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Khabbazi S, Xie N, Pu WJ, Goumon Y, Parat MO (2016) The TLR4-active morphine metabolite morphine-3-glucuronide does not elicit macrophage classical activation in vitro. Front Pharmacol 7:441

  • Kieffer BL, Gaveriaux-Ruff C (2002) Exploring the opioid system by gene knockout. Prog Neurobiol 66:285–306

    Article  CAS  PubMed  Google Scholar 

  • Kohrmann A, Kammerer U, Kapp M, Dietl J, Anacker J (2009) Expression of matrix metalloproteinases (MMPs) in primary human breast cancer and breast cancer cell lines: new findings and review of the literature. BMC Cancer 9:188

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kondraganti S, Mohanam S, Chintala SK, Kin Y, Jasti SL, Nirmala C, Lakka SS, Adachi Y, Kyritsis AP, Ali-Osman F, Sawaya R, Fuller GN, Rao JS (2000) Selective suppression of matrix metalloproteinase-9 in human glioblastoma cells by antisense gene transfer impairs glioblastoma cell invasion. Cancer Res 60:6851–6855

    CAS  PubMed  Google Scholar 

  • Koodie L, Ramakrishnan S, Roy S (2010) Morphine suppresses tumor angiogenesis through a HIF-1alpha/p38MAPK pathway. Am J Pathol 177:984–997

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Koodie L, Yuan H, Pumper JA, Yu H, Charboneau R, Ramkrishnan S, Roy S (2014) Morphine inhibits migration of tumor-infiltrating leukocytes and suppresses angiogenesis associated with tumor growth in mice. Am J Pathol 184:1073–1084

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Kraus J, Borner C, Giannini E, Hollt V (2003) The role of nuclear factor kappaB in tumor necrosis factor-regulated transcription of the human mu-opioid receptor gene. Mol Pharmacol 64:876–884

    Article  CAS  PubMed  Google Scholar 

  • Kuo CK, Hanioka N, Hoshikawa Y, Oguri K, Yoshimura H (1991) Species difference of site-selective glucuronidation of morphine. Aust J Pharm 14:187–193

    CAS  Google Scholar 

  • Kupatt C, Weber C, Wolf DA, Becker BF, Smith TW, Kelly RA (1997) Nitric oxide attenuates reoxygenation-induced ICAM-1 expression in coronary microvascular endothelium: role of NFkappaB. J Mol Cell Cardiol 29:2599–2609

    Article  CAS  PubMed  Google Scholar 

  • Labrie M, St-Pierre Y (2013) Epigenetic regulation of mmp-9 gene expression. Cell Mol Life Sci 70:3109–3124

    Article  CAS  PubMed  Google Scholar 

  • Law PY, Wong YH, Loh HH (2000) Molecular mechanisms and regulation of opioid receptor signaling. Annu Rev Pharmacol Toxicol 40:389–430

    Article  CAS  PubMed  Google Scholar 

  • Law PY, Loh HH, Wei LN (2004) Insights into the receptor transcription and signaling: implications in opioid tolerance and dependence. Neuropharmacology 47(Suppl 1):300–311

    Article  CAS  PubMed  Google Scholar 

  • Lee YJ, Suh SY, Song J, Lee SS, Seo AR, Ahn HY, Lee MA, Kim CM, Klepstad P (2015) Serum and urine concentrations of morphine and morphine metabolites in patients with advanced cancer receiving continuous intravenous morphine: an observational study. BMC Palliat Care 14:53

    Article  PubMed  PubMed Central  Google Scholar 

  • Lennon FE, Mirzapoiazova T, Mambetsariev B, Poroyko VA, Salgia R, Moss J, Singleton PA (2014) The mu opioid receptor promotes opioid and growth factor-induced proliferation, migration and epithelial mesenchymal transition (EMT) in human lung cancer. PLoS One 9:e91577

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Lynch CC, Matrisian LM (2002) Matrix metalloproteinases in tumor-host cell communication. Differentiation 70:561–573

    Article  CAS  PubMed  Google Scholar 

  • Magazine HI, Liu Y, Bilfinger TV, Fricchione GL, Stefano GB (1996) Morphine-induced conformational changes in human monocytes, granulocytes, and endothelial cells and in invertebrate immunocytes and microglia are mediated by nitric oxide. J Immunol 156:4845–4850

    CAS  PubMed  Google Scholar 

  • Marshall HE, Stamler JS (2001) Inhibition of NF-kappa B by S-nitrosylation. Biochemistry 40:1688–1693

    Article  CAS  PubMed  Google Scholar 

  • Matthews JR, Botting CH, Panico M, Morris HR, Hay RT (1996) Inhibition of NF-kappaB DNA binding by nitric oxide. Nucleic Acids Res 24:2236–2242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Mignatti P, Rifkin DB (2000) Nonenzymatic interactions between proteinases and the cell surface: novel roles in normal and malignant cell physiology. Adv Cancer Res 78:103–157

    Article  CAS  PubMed  Google Scholar 

  • Miyamae T, Fukushima N, Misu Y, Ueda H (1993) Delta opioid receptor mediates phospholipase C activation via Gi in Xenopus oocytes. FEBS Lett 333:311–314

    Article  CAS  PubMed  Google Scholar 

  • Nelson AR, Fingleton B, Rothenberg ML, Matrisian LM (2000) Matrix metalloproteinases: biologic activity and clinical implications. J Clin Oncol 18:1135–1149

    Article  CAS  PubMed  Google Scholar 

  • Osborne R, Joel S, Trew D, Slevin M (1990) Morphine and metabolite behavior after different routes of morphine administration: demonstration of the importance of the active metabolite morphine-6-glucuronide. Clin Pharmacol Ther 47:12–19

    Article  CAS  PubMed  Google Scholar 

  • O'Sullivan S, Medina C, Ledwidge M, Radomski MW, Gilmer JF (2014) Nitric oxide-matrix metaloproteinase-9 interactions: biological and pharmacological significance--NO and MMP-9 interactions. Biochim Biophys Acta 1843:603–617

    Article  CAS  PubMed  Google Scholar 

  • Ozawa T, Nakagawa T, Minami M, Satoh M (1999) Supersensitization of the adenylyl cyclase system in Chinese hamster ovary cells co-expressing cloned opioid receptors and Gz, a PTX-insensitive G protein. Neurosci Lett 267:117–120

    Article  CAS  PubMed  Google Scholar 

  • Park SK, Lin HL, Murphy S (1997) Nitric oxide regulates nitric oxide synthase-2 gene expression by inhibiting NF-kappaB binding to DNA. Biochem J 322(Pt 2):609–613

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Peacock J (1999) C. Stein (editor), opioids in pain control—basic and clinical aspects. Br J Anaesth 83:978–979

    Article  Google Scholar 

  • Peng HB, Libby P, Liao JK (1995) Induction and stabilization of I-kappa-B-alpha by nitric-oxide mediates inhibition of Nf-kappa-B. J Biol Chem 270:14214–14219

    Article  CAS  PubMed  Google Scholar 

  • Peng HB, Spiecker M, Liao JK (1998) Inducible nitric oxide: an autoregulatory feedback inhibitor of vascular inflammation. J Immunol 161:1970–1976

    CAS  PubMed  Google Scholar 

  • Piros ET, Prather PL, Loh HH, Law PY, Evans CJ, Hales TG (1995) Ca2+ channel and adenylyl cyclase modulation by cloned mu-opioid receptors in GH3 cells. Mol Pharmacol 47:1041–1049

    CAS  PubMed  Google Scholar 

  • Polakiewicz RD, Schieferl SM, Dorner LF, Kansra V, Comb MJ (1998) A mitogen-activated protein kinase pathway is required for mu-opioid receptor desensitization. J Biol Chem 273:12402–12406

    Article  CAS  PubMed  Google Scholar 

  • Pourshanazari A, Allahtavakoli M, Hassanshahi G (2011) Effects of low-dose morphine on nitric oxide concentration and angiogenesis in two-kidney one clip hypertensive rats. Iran J Basic Med Sci 14:560–567

    CAS  PubMed  PubMed Central  Google Scholar 

  • Prevot V, Rialas CM, Croix D, Salzet M, Dupouy JP, Poulain P, Beauvillain JC, Stefano GB (1998) Morphine and anandamide coupling to nitric oxide stimulates GnRH and CRF release from rat median eminence: neurovascular regulation. Brain Res 790:236–244

    Article  CAS  PubMed  Google Scholar 

  • Qin L, Liao L, Redmond A, Young L, Yuan YH, Chen HW, O'Malley BW, Xu JM (2008) The AIB1 oncogene promotes breast cancer metastasis by activation of PEA3-mediated matrix metalloproteinase 2 (MMP2) and MMP9 expression. Mol Cell Biol 28:5937–5950

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qin T, Huang D, Liu Z, Zhang X, Jia Y, Xian CJ, Li K (2018) Tumor necrosis factor superfamily 15 promotes lymphatic metastasis via upregulation of vascular endothelial growth factor-C in a mouse model of lung cancer. Cancer Sci 109:2469–2478

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Qiu S, Feng Y, LeSage G, Zhang Y, Stuart C, He L, Li Y, Caudle Y, Peng Y, Yin D (2015) Chronic morphine-induced microRNA-124 promotes microglial immunosuppression by modulating P65 and TRAF6. J Immunol 194:1021–1030

    Article  CAS  PubMed  Google Scholar 

  • Rialas CM, Weeks B, Cadet P, Goumon Y, Stefano GB (2000) Nociceptin, endomorphin-1 and-2 do not interact with invertebrate immune and neural mu(3) opiate receptor. Acta Pharmacol Sin 21:516–520

    CAS  PubMed  Google Scholar 

  • Ridnour LA, Windhausen AN, Isenberg JS, Yeung N, Thomas DD, Vitek MP, Roberts DD, Wink DA (2007) Nitric oxide regulates matrix metalloproteinase-9 activity by guanylyl-cyclase-dependent and -independent pathways. Proc Natl Acad Sci U S A 104:16898–16903

    Article  PubMed  PubMed Central  Google Scholar 

  • Roomi MW, Monterrey JC, Kalinovsky T, Rath M, Niedzwiecki A (2009) Patterns of MMP-2 and MMP-9 expression in human cancer cell lines. Oncol Rep 21:1323–1333

    CAS  PubMed  Google Scholar 

  • Roy S, Cain KJ, Chapin RB, Charboneau RG, Barke RA (1998) Morphine modulates NF kappa B activation in macrophages. Biochem Biophys Res Commun 245:392–396

    Article  CAS  PubMed  Google Scholar 

  • Sagar S, Sorbi D, Arbeit LA, Singhal PC (1994) Morphine modulates 72-Kda matrix metalloproteinase. Am J Phys 267:F654–F659

    CAS  Google Scholar 

  • Sato H, Seiki M (1993) Regulatory mechanism of 92-Kda type-iv collagenase gene-expression which is associated with invasiveness of tumor-cells. Oncogene 8:395–405

    CAS  PubMed  Google Scholar 

  • Sawada M, Ichinose M, Stefano GB (1997) Nitric oxide inhibits the dopamine-induced K+ current via guanylate cyclase in Aplysia neurons. J Neurosci Res 50:450–456

    Article  CAS  PubMed  Google Scholar 

  • Schmitz R (1985) Friedrich Wilhelm Serturner and the discovery of morphine. Pharm Hist 27:61–74

    CAS  PubMed  Google Scholar 

  • Schutze S, Wiegmann K, Machleidt T, Kronke M (1995) TNF-induced activation of NF-kappa B. Immunobiology 193:193–203

    Article  CAS  PubMed  Google Scholar 

  • Sekhon BS (2010) Matrix metalloproteinases-an overview. Res Rep Biol 2010(1):1–20

    Google Scholar 

  • Sekkai D, Aillet F, Israel N, Lepoivre M (1998) Inhibition of NF-kappaB and HIV-1 long terminal repeat transcriptional activation by inducible nitric oxide synthase 2 activity. J Biol Chem 273:3895–3900

    Article  CAS  PubMed  Google Scholar 

  • Shariftabrizi A, Nifli AP, Ansari M, Saadat F, Ebrahimkhani MR, Alizadeh N, Nasseh A, Alexaki VI, Dehpour AR, Castanas E, Khorramizadeh MR (2006) Matrix metalloproteinase 2 secretion in WEHI 164 fibrosarcoma cells is nitric oxide-related and modified by morphine. Eur J Pharmacol 530:33–39

    Article  CAS  PubMed  Google Scholar 

  • Shimomura K, Kamata O, Ueki S, Ida S, Oguri K, Yoshimura H, Tsukamoto H (1971) Analgesic effect of morphine glucuronides. Tohoku J Exp Med 105:45–52

    Article  CAS  PubMed  Google Scholar 

  • Shin WS, Hong YH, Peng HB, De Caterina R, Libby P, Liao JK (1996) Nitric oxide attenuates vascular smooth muscle cell activation by interferon-gamma. The role of constitutive NF-kappa B activity. J Biol Chem 271:11317–11324

    Article  CAS  PubMed  Google Scholar 

  • Shin CY, Lee WJ, Choi JW, Choi MS, Ryu JR, Oh SJ, Cheong JH, Choi EY, Ko KH (2007) Down-regulation of matrix metalloproteinase-9 expression by nitric oxide in lipopolysaccharide-stimulated rat primary astrocytes. Nitric Oxide 16:425–432

    Article  CAS  PubMed  Google Scholar 

  • Sinha I, Hannawa KK, Ailawadi G, Woodrum DT, Ford JW, Henke PK, Stanley JC, Eagleton MJ, Upchurch GR Jr (2006) The nitric oxide donor DETA-NONOate decreases matrix metalloproteinase-9 expression and activity in rat aortic smooth muscle and abdominal aortic explants. Ann Vasc Surg 20:92–98

    Article  PubMed  Google Scholar 

  • Stamenkovic I (2003) Extracellular matrix remodelling: the role of matrix metalloproteinases. J Pathol 200:448–464

    Article  CAS  PubMed  Google Scholar 

  • Stefano GB, Hartman A, Bilfinger TV, Magazine HI, Liu Y, Casares F, Goligorsky MS (1995) Presence of the mu(3) opiate receptor in endothelial cells - coupling to nitric oxide production and vasodilation. J Biol Chem 270:30290–30293

    Article  CAS  PubMed  Google Scholar 

  • Stefano GB, Scharrer B, Smith EM, Hughes TK Jr, Magazine HI, Bilfinger TV, Hartman AR, Fricchione GL, Liu Y, Makman MH (1996) Opioid and opiate immunoregulatory processes. Crit Rev Immunol 16:109–144

    Article  CAS  PubMed  Google Scholar 

  • Stefano GB, Salzet B, Rialas CM, Pope M, Kustka A, Neenan K, Pryor S, Salzet M (1997) Morphine- and anandamide-stimulated nitric oxide production inhibits presynaptic dopamine release. Brain Res 763:63–68

    Article  CAS  PubMed  Google Scholar 

  • Stefano GB, Salzet M, Bilfinger TV (1998) Long-term exposure of human blood vessels to HIV gp120, morphine, and anandamide increases endothelial adhesion of monocytes: uncoupling of nitric oxide release. J Cardiovasc Pharmacol 31:862–868

    Article  CAS  PubMed  Google Scholar 

  • Stefano GB, Kream RM, Mantione KJ, Sheehan M, Cadet P, Zhu W, Bilfinger TV, Esch T (2008) Endogenous morphine/nitric oxide-coupled regulation of cellular physiology and gene expression: implications for cancer biology. Semin Cancer Biol 18:199–210

    Article  CAS  PubMed  Google Scholar 

  • Swartz MA, Iida N, Roberts EW, Sangaletti S, Wong MH, Yull FE, Coussens LM, DeClerck YA (2012) Tumor microenvironment complexity: emerging roles in cancer therapy. Cancer Res 72:2473–2480

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Taylor DA, Fleming WW (2001) Unifying perspectives of the mechanisms underlying the development of tolerance and physical dependence to opioids. J Pharmacol Exp Ther 297:11–18

    CAS  PubMed  Google Scholar 

  • Thirlwell MP, Sloan PA, Maroun JA, Boos GJ, Besner JG, Stewart JH, Mount BM (1989) Pharmacokinetics and clinical efficacy of oral morphine solution and controlled-release morphine tablets in cancer patients. Cancer 63:2275–2283

    Article  CAS  PubMed  Google Scholar 

  • van Hinsbergh VW, Engelse MA, Quax PH (2006) Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol 26:716–728

    Article  CAS  PubMed  Google Scholar 

  • Vandooren J, Van den Steen PE, Opdenakker G (2013) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9): the next decade. Crit Rev Biochem Mol Biol 48:222–272

    Article  CAS  PubMed  Google Scholar 

  • Vihinen P, Kahari VM (2002) Matrix metalloproteinases in cancer: prognostic markers and therapeutic targets. Int J Cancer 99:157–166

    Article  CAS  PubMed  Google Scholar 

  • Visse R, Nagase H (2003) Matrix metalloproteinases and tissue inhibitors of metalloproteinases - structure, function, and biochemistry. Circ Res 92:827–839

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Barke RA, Charboneau R, Loh HH, Roy S (2003) Morphine negatively regulates interferon-gamma promoter activity in activated murine T cells through two distinct cyclic AMP-dependent pathways. J Biol Chem 278:37622–37631

    Article  CAS  PubMed  Google Scholar 

  • Wang J, Barke RA, Charboneau R, Roy S (2005) Morphine impairs host innate immune response and increases susceptibility to Streptococcus pneumoniae lung infection. J Immunol 174:426–434

    Article  CAS  PubMed  Google Scholar 

  • Welters ID, Fimiani C, Bilfinger TV, Stefano GB (2000a) NF-kappaB, nitric oxide and opiate signaling. Med Hypotheses 54:263–268

    Article  CAS  PubMed  Google Scholar 

  • Welters ID, Menzebach A, Goumon Y, Cadet P, Menges T, Hughes TK, Hempelmann G, Stefano GB (2000b) Morphine inhibits NF-kappaB nuclear binding in human neutrophils and monocytes by a nitric oxide-dependent mechanism. Anesthesiology 92:1677–1684

    Article  CAS  PubMed  Google Scholar 

  • Widel MS, Widel M (2006) Mechanisms of metastasis and molecular markers of malignant tumor progression. I. Colorectal cancer. Postepy Hig Med Dosw (Online) 60:453–470

    Google Scholar 

  • Wink DA, Hines HB, Cheng RY, Switzer CH, Flores-Santana W, Vitek MP, Ridnour LA, Colton CA (2011) Nitric oxide and redox mechanisms in the immune response. J Leukoc Biol 89:873–891

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Xie N, Khabbazi S, Nassar ZD, Gregory K, Vithanage T, Anand-Apte B, Cabot PJ, Sturgess D, Shaw PN, Parat MO (2017) Morphine alters the circulating proteolytic profile in mice: functional consequences on cellular migration and invasion. FASEB J 31:5208–5216

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Yabluchanskiy A, Ma YG, Iyer RP, Hall ME, Lindsey ML (2013) Matrix metalloproteinase-9: many shades of function in cardiovascular disease. Physiology 28:391–403

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  • Ye RD (2001a) Regulation of nuclear factor kappa B activation by G-protein-coupled receptors. J Leukoc Biol 70:839–848

    CAS  PubMed  Google Scholar 

  • Ye RD (2001b) Regulation of nuclear factor kappaB activation by G-protein-coupled receptors. J Leukoc Biol 70:839–848

    CAS  PubMed  Google Scholar 

  • Zouki C, Jozsef L, Ouellet S, Paquette Y, Filep JG (2001) Peroxynitrite mediates cytokine-induced IL-8 gene expression and production by human leukocytes. J Leukoc Biol 69:815–824

    CAS  PubMed  Google Scholar 

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Funding

Authors’ own work discussed was supported in part by National Health and Medical Research Council Australia (NHMRC) project grants and fellowships (numbers 0508046, 0508047 and 1042105).

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  1. Samira Khabbazi and Mohammadhossein Hassanshahi contributed equally to this work.

Authors and Affiliations

  1. School of Medical Science, The South Australian Health and Medical Research Institute, The University of Adelaide, Adelaide, SA, 5001, Australia

    Samira Khabbazi

  2. School of Pharmacy and Medical Sciences, and University of South Australia Cancer Research Institute, University of South Australia, GPO Box 2471, Adelaide, SA 5001, Australia

    Mohammadhossein Hassanshahi, Yaser Peymanfar, Yu-Wen Su & Cory J. Xian

  3. Department of Genetics, Faculty of Basic Sciences, Islamic Azad University, Shahrekord, Iran

    Alireza Hassanshahi

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  1. Samira Khabbazi
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  3. Alireza Hassanshahi
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SK and MH designed and conducted the literature review and drafted the manuscript. AH, PY and YS conducted the literature review. CJX designed and conceptualised the manuscript.

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Correspondence to Cory J. Xian.

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Khabbazi, S., Hassanshahi, M., Hassanshahi, A. et al. Opioids and matrix metalloproteinases: the influence of morphine on MMP-9 production and cancer progression. Naunyn-Schmiedeberg's Arch Pharmacol 392, 123–133 (2019). https://doi.org/10.1007/s00210-019-01613-6

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