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Increased expression of ADAM family members in human breast cancer and breast cancer cell lines

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Abstract

Purpose

ADAMs (A Disintegrin and Metalloprotease) are multifunctional, membrane-bound cell surface glycoproteins, which have numerous functions in cell growth, differentiation, and motility. We wished to investigate the expression of ADAM 9, 10, 12, 15, and in human breast cancer.

Methods

Expression of ADAMs was determined in breast cancer specimens and the corresponding non-neoplastic breast tissue from 24 patients, and in the MCF-7 and MDA-MB 453 breast cancer cell lines via quantitative RT-PCR and immunohistochemistry. The effects of anti-ADAM antibodies on cell proliferation were assessed by measuring DNA-synthesis.

Results

Breast cancer tissue samples showed increased mRNA expression of ADAM 9, 12, and 17, whereas ADAM 10 and 15 were not differently expressed. Protein expression was studied by immunohistochemistry. All ADAMs were expressed in MCF-7 and MDA-MB453 cell lines, with the highest expression levels being observed for ADAM 9, 12, and 17. Application of anti-ADAM 15 and anti-ADAM 17 antibodies significantly inhibited the proliferation of both MCF-7 and MDA-MB453 breast cancer cell lines. In contrast, the growth of MCF-7 cells appeared to be stimulated by the administration of anti-ADAM 12 antibody.

Conclusion

The results of this study suggest that ADAMs are differentially expressed in human breast cancer and are capable of modulating tumour cell growth.

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References

  • Ansorge S, Reinhold D, Lendeckel U (2003) Propolis and some of its constituents down-regulate DNA synthesis and inflammatory cytokine production but induce TGF-beta1 production of human immune cells. Z Naturforsch 58:580–589

    CAS  Google Scholar 

  • Asai M, Hattori C, Szabo B, Sasagawa N, Maruyama K, Tanuma S, Ishiura S (2003) Putative function of ADAM9, ADAM10, and ADAM17 as APP alpha-secretase. Biochem Biophys Res Commun 301:231–235

    Article  CAS  PubMed  Google Scholar 

  • Black RA and White J M (1998) ADAMs: focus on the protease domain. Curr Opin Cell Biol 10:654–659

    Article  CAS  PubMed  Google Scholar 

  • Black RA, Rauch CT, Kozlosky CJ, Peschon JJ, Slack JL, Wolfson MF, Castner BJ, Stocking KL, Reddy P, Srinivasan S, Nelson N, Boiani N, Schooley KA, Gerhart M, Davis R, Fitzner JN, Johnson RS, Paxton RJ, March CJ, Cerretti DP (1997) A metalloproteinase disintegrin that releases tumour-necrosis factor-alpha from cells. Nature 385:729–733

    Article  CAS  PubMed  Google Scholar 

  • Borrell-Pages M, Rojo F, Albanell J, Baselga J, Arribas J (2003) TACE is required for the activation of the EGFR by TGF-alpha in tumors. EMBO J 22:1114–1124

    Article  CAS  PubMed  Google Scholar 

  • Buxbaum JD, Liu KN, Luo Y, Slack JL, Stocking KL, Peschon JJ, Johnson RS, Castner BJ, Cerretti DP, Black RA (1998) Evidence that tumor necrosis factor alpha converting enzyme is involved in regulated alpha-secretase cleavage of the Alzheimer amyloid protein precursor. J Biol Chem 273:27765–27767

    Article  CAS  PubMed  Google Scholar 

  • Cruz AC, Frank BT, Edwards ST, Dazin PF, Peschon JJ, Fang KC (2004) Tumor necrosis factor-alpha converting enzyme controls surface expression of c-Kit and survival of embryonic stem cell-derived mast cells. J Biol Chem 279:5612–5620

    Article  CAS  PubMed  Google Scholar 

  • Eccles SA (2001) The role of c-erbB-2/HER2/neu in breast cancer progression and metastasis. J Mammary Gland Biol Neoplasia 6:393–406

    Article  CAS  PubMed  Google Scholar 

  • Filardo EJ (2002) Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer. J Steroid Biochem Mol Biol 80:231–238

    Article  CAS  PubMed  Google Scholar 

  • Fischer OM, Hart S, Gschwind A, Ullrich A (2003) EGFR signal transactivation in cancer cells. Biochem Soc Trans 31:1203–1208

    CAS  PubMed  Google Scholar 

  • Garton KJ, Gough PJ, Blobel CP, Murphy G, Greaves DR, Dempsey PJ, Raines EW (2001) Tumor necrosis factor-alpha-converting enzyme (ADAM17) mediates the cleavage and shedding of fractalkine (CX3CL1). J Biol Chem 276:37993–38001

    CAS  PubMed  Google Scholar 

  • Gee JM, Knowlden JM (2003) ADAM metalloproteases and EGFR signalling. Breast Cancer Res 5:223–224

    Article  CAS  PubMed  Google Scholar 

  • Guo L, Eisenman JR, Mahimkar RM, Peschon JJ, Paxton RJ, Black RA, Johnson RS (2002) A proteomic approach for the identification of cell-surface proteins shed by metalloproteases. Mol Cell Proteomics 1:30–36

    Article  CAS  PubMed  Google Scholar 

  • Iba K, Albrechtsen R, Gilpin B, Frohlich C, Loechel F, Zolkiewska A, Ishiguro K, Kojima T, Liu W, Langford JK, Sanderson RD, Brakebusch C, Fassler R, Wewer UM (2000) The cysteine-rich domain of human ADAM 12 supports cell adhesion through syndecans and triggers signaling events that lead to beta1 integrin-dependent cell spreading. J Cell Biol 149:1143–1156

    Article  CAS  PubMed  Google Scholar 

  • Juhasz M, Chen J, Lendeckel U, Kellner U, Kasper HU, Tulassay Z, Pastorekova S, Malfertheiner P, Ebert MP (2003) Expression of carbonic anhydrase IX in human pancreatic cancer. Aliment Pharmacol Ther 18:837–846

    Article  CAS  PubMed  Google Scholar 

  • Le Pabic H, Bonnier D, Wewer UM, Coutand A, Musso O, Baffet G, Clement B, Theret N (2003) ADAM12 in human liver cancers: TGF-beta-regulated expression in stellate cells is associated with matrix remodeling. Hepatology 37:1056–1066

    Article  PubMed  Google Scholar 

  • Millichip MI, Dallas DJ, Wu E, Dale S, McKie N (1998) The metallo-disintegrin ADAM10 (MADM) from bovine kidney has type IV collagenase activity in vitro. Biochem Biophys Res Commun 245:594–598

    Article  CAS  PubMed  Google Scholar 

  • Nath D, Slocombe PM, Stephens PE, Warn A, Hutchinson GR, Yamada KM, Docherty AJ, Murphy G (1999) Interaction of metargidin (ADAM-15) with alphavbeta3 and alpha5beta1 integrins on different haemopoietic cells. J Cell Sci 112:579–587

    CAS  PubMed  Google Scholar 

  • Nath D, Slocombe PM, Webster A, Stephens PE, Docherty AJ, Murphy G (2000) Meltrin gamma(ADAM-9) mediates cellular adhesion through alpha(6)beta(1)integrin, leading to a marked induction of fibroblast cell motility. J Cell Sci 113:2319–2328

    CAS  PubMed  Google Scholar 

  • O’Shea C, McKie N, Buggy Y, Duggan C, Hill AD, McDermott E, O’Higgins N, Duffy MJ (2003) Expression of ADAM-9 mRNA and protein in human breast cancer. Int J Cancer 105:754–761

    Article  PubMed  Google Scholar 

  • Persad S, Dedhar S (2003) The role of integrin-linked kinase (ILK) in cancer progression. Cancer Metastasis Rev 22:375–384

    Article  CAS  PubMed  Google Scholar 

  • Peschon JJ, Slack JL, Reddy P, Stocking KL, Sunnarborg SW, Lee DC, Russell WE, Castner BJ, Johnson RS, Fitzner JN, Boyce RW, Nelson N, Kozlosky CJ, Wolfson MF, Rauch CT, Cerretti DP, Paxton RJ, March CJ, Black RA (1998) An essential role for ectodomain shedding in mammalian development. Science 282:1281–1284

    Article  CAS  PubMed  Google Scholar 

  • Quaranta V, Giannelli G (2003) Cancer invasion: watch your neighbourhood! Tumori 89:343–348

    Google Scholar 

  • Schlondorff J, Blobel CP (1999) Metalloprotease-disintegrins: modular proteins capable of promoting cell-cell interactions and triggering signals by protein-ectodomain shedding. J Cell Sci 112:3603–3617

    CAS  PubMed  Google Scholar 

  • Schuppan D, Ocker M (2003) Integrin-mediated control of cell growth. Hepatology 38:289–291

    Article  PubMed  Google Scholar 

  • Tian BL, Wen JM, Zhang M, Xie D, Xu RB, Luo CJ (2002) The expression of ADAM12 (meltrin alpha) in human giant cell tumours of bone. Mol Pathol 55:394–397

    Article  CAS  PubMed  Google Scholar 

  • Tomczuk M, Takahashi Y, Huang J, Murase S, Mistretta M, Klaffky E, Sutherland A, Bolling L, Coonrod S, Marcinkiewicz C, Sheppard D, Stepp MA, White JM (2003) Role of multiple beta1 integrins in cell adhesion to the disintegrin domains of ADAMs 2 and 3. Exp Cell Res 290:68–81

    Article  CAS  PubMed  Google Scholar 

  • Tselepis VH, Green LJ, Humphries MJ (1997) An RGD to LDV motif conversion within the disintegrin kistrin generates an integrin antagonist that retains potency but exhibits altered receptor specificity. Evidence for a functional equivalence of acidic integrin-binding motifs. J Biol Chem 272:21341–21348

    Article  CAS  PubMed  Google Scholar 

  • Tsou CL, Haskell CA, Charo IF (2001) Tumor necrosis factor-alpha-converting enzyme mediates the inducible cleavage of fractalkine. J Biol Chem 276:44622–44626

    Article  CAS  PubMed  Google Scholar 

  • Tucker GC (2003) Alpha v integrin inhibitors and cancer therapy. Curr Opin Investig Drugs 4:722–731

    CAS  PubMed  Google Scholar 

  • Wang X, He K, Gerhart M, Huang Y, Jiang J, Paxton RJ, Yang S, Lu C, Menon RK, Black RA, Baumann G, Frank SJ (2002) Metalloprotease-mediated GH receptor proteolysis and GHBP shedding. Determination of extracellular domain stem region cleavage site. J Biol Chem 277:50510–50519

    Article  CAS  PubMed  Google Scholar 

  • Werb Z, Yan Y (1998) A cellular striptease act. Science 282:1279–1280

    Article  CAS  PubMed  Google Scholar 

  • Wolfsberg TG, Primakoff P, Myles DG, White JM (1995) ADAM, a novel family of membrane proteins containing A Disintegrin And Metalloprotease domain: multipotential functions in cell-cell and cell-matrix interactions. J Cell Biol 131:275–278

    Article  CAS  PubMed  Google Scholar 

  • Yoshimura T, Tomita T, Dixon MF, Axon ATR, Robinson PA, Crabtree JE (2002) ADAMs (A Disintegrin and Metalloprotease) messenger RNA expression in Helicobacter pylori-infected, normal, and neoplastic gastric mucosa. J Infect Dis 185:332–340

    Article  CAS  PubMed  Google Scholar 

  • Zhang XP, Kamata T, Yokoyama K, Puzon-McLaughlin W, Takada Y (1998) Specific interaction of the recombinant disintegrin-like domain of MDC-15 (metargidin, ADAM-15) with integrin alphavbeta3. J Biol Chem 273:7345–7350

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We are very grateful to Katja Mook and Cornelia Müller for their excellent technical assistance. We thank Christa Willgeroth and Eckhard Lenz for histological examination. This work was supported in part by the Kultusministerium Sachsen-Anhalt (grant 1071A0086H)

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Correspondence to Uwe Lendeckel.

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Lendeckel, U., Kohl, J., Arndt, M. et al. Increased expression of ADAM family members in human breast cancer and breast cancer cell lines. J Cancer Res Clin Oncol 131, 41–48 (2005). https://doi.org/10.1007/s00432-004-0619-y

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  • DOI: https://doi.org/10.1007/s00432-004-0619-y

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