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Laminin induces matrix metalloproteinase-9 expression and activation in human cervical cancer cell line (SiHa)

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Abstract

Purpose

Interaction between cell surface integrin receptors and extracellular matrix (ECM) components plays an important role in cell survival, proliferation and migration including tumor development and invasion. Matrix metalloproteinases (MMP) are a family of metalloproteinases capable of digesting ECM and facilitate cell migration. Binding of ECM to integrins initiates signaling cascades modulating expression and activity of different MMPs. The present study investigates whether laminin-mediated signaling modulates matrix metalloproteinases (MMP) expression and activity in human cervical cancer cell (SiHa).

Methods

Western blot, immunocytochemistry, ELISA, zymography, RT–PCR, EMSA and wound-healing assay were used.

Results

Culture of SiHa cells on laminin (LN)-coated surface induces MMP-9 expression and activation. Wound-healing assay showed that SiHa cells migrate much faster on laminin-coated surface than that of control. LN-induced MMP-9 expression and activation was appreciably reduced with treatment of extracellular signal–regulated kinase (ERK) inhibitor, phosphatidylinositol-3-kinase (PI-3K) inhibitor and anti-α2 antibody. Phosphorylation of focal adhesion kinase (FAK), ERK, and PI-3K was increased upon LN stimulation. LN induces nuclear translocation of PI-3K and nuclear factor kappa B (NF-κB). LN increases DNA-binding activity of NF-κB and activator protein-1 (AP-1) to MMP-9 promoter.

Conclusions

Our findings indicate laminin-induced MMP-9 expression and activation possibly via α2β1 integrin-mediated signaling involving FAK, PI-3K, ERK followed by transcriptional upregulation of MMP-9.

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References

  • Aicher WK, Pap T, Gay S (2008) Laminin-dependent inflammatory response in synovial fibroblasts of rheumatoid arthritis patients. Z Rheumatol 67:59–61

    Article  CAS  PubMed  Google Scholar 

  • Avraamides CJ, Garmy-Susini B, Varner JA (2008) Integrins in angiogenesis and lymphangiogenesis. Nat Rev Cancer 8:604–617

    Article  CAS  PubMed  Google Scholar 

  • Baba Y, Iyama KI, Hirashima K, Nagai Y, Yoshida N, Hayashi N, Miyanari N, Baba H (2008) Laminin-332 promotes the invasion of oesophageal squamous cell carcinoma via PI3K activation. Br J Cancer 98:974–980

    Article  CAS  PubMed  Google Scholar 

  • Brakebusch C, Bouvard D, Stanchi F, Sakai T, Fassler R (2002) Intergins in invasive growth. J Clin Invest 109:999–1006

    CAS  PubMed  Google Scholar 

  • Brew K, Dinakarpandian D, Nagase H (2000) Tissue inhibitors of metalloproteinases: evolution, structure and function. Biochim Biophys Acta 1477:267–283

    Article  CAS  PubMed  Google Scholar 

  • Das S, Banerji A, Frei E, Chatterjee A (2008) Rapid expression and activation of MMP-2 and MMP-9 upon exposure of human breast cancer cells (MCF-7) to fibronectin in serum free medium. Life Sci 82:467–476

    Article  CAS  PubMed  Google Scholar 

  • Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34

    Article  CAS  PubMed  Google Scholar 

  • DiPersio CM, Shao M, Di Costanzo L, Kreidberg JA, Hynes RO (2000) Mouse keratinocytes immortalized with large T antigen acquire alpha3beta1 integrin-dependent secretion of MMP-9/gelatinase B. J Cell Sci 113(Pt 16):2909–2921

    CAS  PubMed  Google Scholar 

  • Ekblom P, Lonai P, Talts JF (2003) Expression and biological role of laminin-1. Matrix Biol

  • Freitas VM, Vilas-Boas VF, Pimenta DC, Loureiro V, Juliano MA, Carvalho MR, Pinheiro JJ, Camargo AC, Moriscot AS, Hoffman MP, Jaeger RG (2007) SIKVAV, a laminin alpha1-derived peptide, interacts with integrins and increases protease activity of a human salivary gland adenoid cystic carcinoma cell line through the ERK 1/2 signaling pathway. Am J Pathol 171:124–138

    Article  CAS  PubMed  Google Scholar 

  • Givant-Horwitz V, Davidson B, Reich R (2005) Laminin-induced signaling in tumor cells. Cancer Lett 223:1–10

    Article  CAS  PubMed  Google Scholar 

  • Grenache DG, Zhang Z, Wells LE, Santoro SA, Davidson JM, Zutter MM (2007) Wound healing in the alpha2beta1 integrin-deficient mouse: altered keratinocyte biology and dysregulated matrix metalloproteinase expression. J Invest Dermatol 127:455–466

    Article  CAS  PubMed  Google Scholar 

  • Gu J, Fujibayashi A, Yamada KM, Sekiguchi K (2002a) Laminin-10/11 and fibronectin differentially prevent apoptosis induced by serum removal via phosphatidylinositol 3-kinase/Akt- and MEK1/ERK-dependent pathways. J Biol Chem 277:19922–19928

    Article  CAS  PubMed  Google Scholar 

  • Gu J, Nishiuchi R, Sekiguchi K (2002b) Matrix metalloproteinase-2 is involved in A549 cell migration on laminin-10/11. Biochem Biophys Res Commun 296:73–77

    Article  CAS  PubMed  Google Scholar 

  • Han S, Ritzenthaler JD, Sitaraman SV, Roman J (2006) Fibronectin increases matrix metalloproteinase 9 expression through activation of c-Fos via extracellular-regulated kinase and phosphatidylinositol 3-kinase pathways in human lung carcinoma cells. J Biol Chem 281:29614–29624

    Article  CAS  PubMed  Google Scholar 

  • Hannigan G, Troussard AA, Dedhar S (2005) Integrin-linked kinase: a cancer therapeutic target unique among its ILK. Nat Rev Cancer 5:51–63

    Article  CAS  PubMed  Google Scholar 

  • Jung SH, Woo MS, Kim SY, Kim WK, Hyun JW, Kim EJ, Kim DH, Kim HS (2006) Ginseng saponin metabolite suppresses phorbol ester-induced matrix metalloproteinase-9 expression through inhibition of activator protein-1 and mitogen-activated protein kinase signaling pathways in human astroglioma cells. Int J Cancer 118:490–497

    Article  CAS  PubMed  Google Scholar 

  • Khan KM, Falcone DJ, Kraemer R (2002) Nerve growth factor activation of Erk-1 and Erk-2 induces matrix metalloproteinase-9 expression in vascular smooth muscle cells. J Biol Chem 277:2353–2359

    Article  CAS  PubMed  Google Scholar 

  • Kubota S, Tashiro K, Yamada Y (1992) Signaling site of laminin with mitogenic activity. J Biol Chem 267:4285–4288

    CAS  PubMed  Google Scholar 

  • Kuratomi Y, Nomizu M, Tanaka K, Ponce ML, Komiyama S, Kleinman HK, Yamada Y (2002) Laminin gamma 1 chain peptide, C-16 (KAFDITYVRLKF), promotes migration, MMP-9 secretion, and pulmonary metastasis of B16–F10 mouse melanoma cells. Br J Cancer 86:1169–1173

    Article  CAS  PubMed  Google Scholar 

  • Lochter A, Navre M, Werb Z, Bissell MJ (1999) Alpha1 and alpha2 integrins mediate invasive activity of mouse mammary carcinoma cells through regulation of stromelysin-1 expression. Mol Biol Cell 10:271–282

    CAS  PubMed  Google Scholar 

  • Maity G, Fahreen S, Banerji A, Roy Choudhury P, Sen T, Dutta A, Chatterjee A (2010) Fibronectin-integrin mediated signaling in human cervical cancer cells (SiHa). Mol Cell Biochem 336:65–74

    Article  CAS  PubMed  Google Scholar 

  • Menard S, Tagliabue E, Colnaghi MI (1998) The 67 kDa laminin receptor as a prognostic factor in human cancer. Breast Cancer Res Treat 52:137–145

    Article  CAS  PubMed  Google Scholar 

  • Mitra A, Chakrabarti J, Banerji A et al (2006) Culture of human cervical cancer cells, SiHa, in the presence of fibronectin activates MMP-2. J Cancer Res Clin Oncol 132:505–513

    Article  CAS  PubMed  Google Scholar 

  • Neri LM, Milani D, Bertolaso L, Stroscio M, Bertagnolo V, Capitani S (1994) Nuclear translocation of phosphatidylinositol 3-kinase in rat pheochromocytoma PC 12 cells after treatment with nerve growth factor. Cell Mol Biol (Noisy-le-grand) 40:619–626

    CAS  Google Scholar 

  • Newell KJ, Witty JP, Rodgers WH, Matrisian LM (1994) Expression and localization of matrix-degrading metalloproteinases during colorectal tumorigenesis. Mol Carcinog 10:199–206

    Article  CAS  PubMed  Google Scholar 

  • Patarroyo M, Tryggvason K, Virtanen I (2002) Laminin isoforms in tumor invasion, angiogenesis and metastasis. Semin Cancer Biol 12:197–207

    Article  CAS  PubMed  Google Scholar 

  • Reich R, Blumenthal M, Liscovitch M (1995) Role of phospholipase D in laminin-induced production of gelatinase A (MMP-2) in metastatic cells. Clin Exp Metastasis 13:134–140

    Article  CAS  PubMed  Google Scholar 

  • Sang QX, Birkedal-Hansen H, Van Wart HE (1995) Proteolytic and non-proteolytic activation of human neutrophil progelatinase B. Biochim Biophys Acta 1251:99–108

    Article  PubMed  Google Scholar 

  • Sawhney RS, Cookson MM, Omar Y, Hauser J, Brattain MG (2006) Integrin alpha2-mediated ERK and calpain activation play a critical role in cell adhesion and motility via focal adhesion kinase signaling: identification of a novel signaling pathway. J Biol Chem 281:8497–8510

    Article  CAS  PubMed  Google Scholar 

  • Sen T, Moulik S, Dutta A, Choudhury PR, Banerji A, Das S, Roy M, Chatterjee A (2009) Multifunctional effect of epigallocatechin-3-gallate (EGCG) in downregulation of gelatinase-A (MMP-2) in human breast cancer cell line MCF-7. Life Sci 84:194–204

    Article  CAS  PubMed  Google Scholar 

  • Stack S, Gray RD, Pizzo SV (1991) Modulation of plasminogen activation and type IV collagenase activity by a synthetic peptide derived from the laminin A chain. Biochemistry 30:2073–2077

    Article  CAS  PubMed  Google Scholar 

  • Takahra T, Smart DE, Oakley F, Mann DA (2004) Induction of myofibroblast MMP-9 transcription in three-dimensional collagen I gel cultures: regulation by NF-kappaB, AP-1 and Sp1. Int J Biochem Cell Biol 36:353–363

    Article  CAS  PubMed  Google Scholar 

  • Toth M, Chvyrkova I, Bernardo MM, Hernandez-Barrantes S, Fridman R (2003) Pro-MMP-9 activation by the MT1-MMP/MMP-2 axis and MMP-3: role of TIMP-2 and plasma membranes. Biochem Biophys Res Commun 308:386–395

    Article  CAS  PubMed  Google Scholar 

  • Troussard AA, Costello P, Yoganathan TN, Kumagai S, Roskelley CD, Dedhar S (2000) The integrin linked kinase (ILK) induces an invasive phenotype via AP-1 transcription factor-dependent upregulation of matrix metalloproteinase 9 (MMP-9). Oncogene 19:5444–5452

    Article  CAS  PubMed  Google Scholar 

  • Van den Steen PE, Dubois B, Nelissen I, Rudd PM, Dwek RA, Opdenakker G (2002) Biochemistry and molecular biology of gelatinase B or matrix metalloproteinase-9 (MMP-9). Crit Rev Biochem Mol Biol 37:375–536

    Article  PubMed  Google Scholar 

  • Wang YG, Ji X, Pabbidi M, Samarel AM, Lipsius SL (2009) Laminin acts via focal adhesion kinase/phosphatidylinositol-3′ kinase/protein kinase B to down-regulate beta1-adrenergic receptor signalling in cat atrial myocytes. J Physiol 587:541–550

    Article  CAS  PubMed  Google Scholar 

  • Waterman EA, Sakai N, Nguyen NT, Horst BA, Veitch DP, Dey CN, Ortiz-Urda S, Khavari PA, Marinkovich MP (2007) A laminin-collagen complex drives human epidermal carcinogenesis through phosphoinositol-3-kinase activation. Cancer Res 67:4264–4270

    Article  CAS  PubMed  Google Scholar 

  • Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. Faseb J 13:781–792

    CAS  PubMed  Google Scholar 

  • Yao J, Xiong S, Klos K, Nguyen N, Grijalva R, Li P, Yu D (2001) Multiple signaling pathways involved in activation of matrix metalloproteinase-9 (MMP-9) by heregulin-beta1 in human breast cancer cells. Oncogene 20:8066–8074

    Article  CAS  PubMed  Google Scholar 

  • Zahir N, Lakins JN, Russell A, Ming W, Chatterjee C, Rozenberg GI, Marinkovich MP, Weaver VM (2003) Autocrine laminin-5 ligates alpha6beta4 integrin and activates RAC and NFkappaB to mediate anchorage-independent survival of mammary tumors. J Cell Biol 163:1397–1407

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgments

We acknowledge Director, Chittaranjan National Cancer Institute for Institute facilities, financial support and Department of Science and Technology, New Delhi (Grant No. SR/SO/HS-59/2004) for financial support.

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Authors and Affiliations

  1. Department of Receptor Biology and Tumor Metastasis, Chittaranjan National Cancer Institute, 37, S. P. Mukherjee Road, Kolkata, West Bengal, 700026, India

    Gargi Maity, Triparna Sen & Amitava Chatterjee

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  1. Gargi Maity
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  2. Triparna Sen
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  3. Amitava Chatterjee
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Correspondence to Amitava Chatterjee.

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Maity, G., Sen, T. & Chatterjee, A. Laminin induces matrix metalloproteinase-9 expression and activation in human cervical cancer cell line (SiHa). J Cancer Res Clin Oncol 137, 347–357 (2011). https://doi.org/10.1007/s00432-010-0892-x

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  • DOI: https://doi.org/10.1007/s00432-010-0892-x

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