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2012 | 59 | 4 | 593-598
Article title

S100A4 promotes invasion and angiogenesis in breast cancer MDA-MB-231 cells by upregulating matrix metalloproteinase-13

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EN
Abstracts
EN
S100A4 is a member of the S100 family of calcium-binding proteins that is directly involved in tumor metastasis. In the present study, we examined the potential role of S100A4 in metastasis in breast cancer and its relation with matrix metalloproteinase-13 (MMP-13). Analysis of 100 breast cancer specimens including 50 with and 50 without lymph node metastasis showed a significant upregulation of S100A4 and MMP-13 expression in metastatic breast cancer tissues. Positive immunoreactivity for S100A4 was associated with MMP-13 expression. Overexpression of S100A4 in the MDA-MB-231 breast cancer cell line upregulated MMP13 expression leading to increased cell migration and angiogenesis. SiRNA-mediated silencing of S100A4 downregulated MMP13 expression and suppressed cell migration and angiogenesis. Moreover, neutralization of MMP-13 activity with a specific antibody blocked cell migration and angiogenesis in MDA-MB-231/S100A4 cells. In vivo siRNA silencing of S100A4 significantly inhibited lung metastasis in transgenic mice. The present results suggest that the S100A4 gene may control the invasive potential of human breast cancer cells by modulating MMP-13 levels, thus regulating metastasis and angiogenesis in breast tumors. S100A4 could therefore be of value as a biomarker of breast cancer progression and a novel therapeutic target for human breast cancer treatment.
Keywords
Publisher

Year
Volume
59
Issue
4
Pages
593-598
Physical description
Dates
published
2012
received
2012-03-29
revised
2012-07-03
accepted
2012-10-24
(unknown)
2012-11-16
Contributors
author
  • Department of Breast and Thyroid Diseases, Tianjin Union Medicine Centre, Tianjin, China
author
  • Breast Surgery, the Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, R.P.China
author
  • Breast Surgery, the Second Hospital of Tianjin Medical College, Tianjin, R.P.China
author
  • Breast Surgery, the Second Hospital of Tianjin Medical College, Tianjin, R.P.China
author
  • Breast Surgery, the Affiliated Hospital of Qingdao Medical College, Qingdao University, Qingdao, R.P.China
References
  • Ambartsumian N, Klingelhöfer J, Grigorian M, Christensen C, Kriajevska M, Tulchinsky E, Georgiev G, Berezin V, Bock E, Rygaard J, Cao R, Cao Y, Lukanidin E (2001) The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor. Oncogene 20: 4685-4695.
  • Ambartsumian NS, Grigorian MS, Larsen IF, Karlstrøm O, Sidenius N, Rygaard J, Georgiev G, Lukanidin E (1996) Metastasis of mammary carcinomas in GRS/A hybrid mice transgenic for the mts1 gene. Oncogene 13: 1621-1630.
  • Acuff HB, Carter KJ, Fingleton B, Gorden DL, Matrisian LM (2006) Matrix metalloproteinase-9 from bone marrow-derived cells contributes to survival but not growth of tumor cells in the lung microenvironment. Cancer Res 66: 259-266.
  • Duarte WR, Shibata T, Takenaga K, Takahashi E, Kubota K, Ohya K, Ishikawa I, Yamauchi M, Kasugai S (2003) S100A4: a novel negative regulator of mineralization and osteoblast differentiation. J Bone Miner Res 18: 493-501.
  • Davies BR, Davies MP, Gibbs FE, Barraclough R, Rudland PS (1993) Induction of the metastatic phenotype by transfection of a benign rat mammary epithelial cell line with the gene for p9Ka, a rat calcium-binding protein, but not with the oncogene EJ-ras-1. Oncogene 8: 999-1008.
  • Ford HL, Zain SB (1995) Interaction of metastasis associated Mts1 protein with nonmuscle myosin. Oncogene 10: 1597-1605.
  • Freije JM, Díez-Itza I, Balbín M, Sánchez LM, Blasco R, Tolivia J, López-Otín C (1994) Molecular cloning and expression of collagenase-3, a novel human matrix metalloproteinase produced by breast carcinomas. J Biol Chem 269: 16766-1673.
  • Grigorian M, Ambartsumian N, Lykkesfeldt AE, Bastholm L, Elling F, Georgiev G, Lukanidin E (1996) Effect of mts1 (S100A4) expression on the progression of human breast cancer cells. Int J Cancer 67: 831-841.
  • Garrett SC, Varney KM, Weber DJ, Bresnick AR (2006) S100A4, a mediator of metastasis. J Biol Chem 281: 677-680.
  • Ismail NI, Kaur G, Hashim H, Hassan MS (2010) S100A4 overexpression proves to be independent marker for breast cancer progression. Cancer Cell Int 8: 12.
  • Jenkinson SR, Barraclough R, West CR, Rudland PS (2004) S100A4 regulates cell motility and invasion in an in vitro model for breast cancer metastasis. Br J Cancer 90: 253-262.
  • Klingelhöfer J, Ambartsumian NS, Lukanidin EM (1997) Expression of the metastasis-associated mts1 gene during mouse development. Dev Dyn 210: 87-95.
  • Levett D, Flecknell PA, Rudland PS, Barraclough R, Neal DE, Mellon JK, Davies BR (2002) Transfection of S100A4 produces metastatic variants of an orthotopic model of bladder cancer. Am J Pathol 160: 693-700.
  • Liu X, Li F, Sun SQ, Thangavel M, Kaminsky J, Balazs L, Ostrom RS (2010) Fibroblast-specific expression of AC6 enhances beta-adrenergic and prostacyclin signaling and blunts bleomycin-induced pulmonary fibrosis. Am J Physiol Lung Cell Mol Physiol 298: L819-L829.
  • Lloyd BH, Platt-Higgins A, Rudland PS, Barraclough R (1998) Human S100A4 (p9Ka) induces the metastatic phenotype upon benign tumour cells. Oncogene 17: 465-473.
  • Malashkevich VN, Varney KM, Garrett SC, Wilder PT, Knight D, Charpentier TH, Ramagopal UA, Almo SC, Weber DJ, Bresnick AR (2008) Structure of Ca2+-bound S100A4 and its interaction with peptides derived from nonmuscle myosin-IIA. Biochemistry 47: 5111-5126.
  • Maelandsmo GM, Hovig E, Skrede M, Engebraaten O, Flørenes VA, Myklebost O, Grigorian M, Lukanidin E, Scanlon KJ, Fodstad O (1996) Reversal of the in vivo metastatic phenotype of human tumor cells by an anti-CAPL (mts1) ribozyme. Cancer Res 56: 5490-5498.
  • Matsuura I, Lai CY, Chiang KN (2010) Functional interaction between Smad3 and S100A4 (metastatin-1) for TGF-β-mediated cancer cell invasiveness. Biochem J 426: 327-335.
  • McKay JA, Douglas JJ, Ross VG (2002) Analysis of key cell cycle checkpoint proteins in colorectal tumours. J Pathol 196: 386-393.
  • Neutzner M, Lopez T, Feng X, Bergmann-Leitner ES, Leitner WW, Udey MC (2007) MFG-E8/lactadherin promotes tumor growth in an angiogenesis-dependent transgenic mouse model of multistage carcinogenesis. Cancer Res 67: 6777-6785.
  • Novitskaya V, Grigorian M, Kriajevska M, Tarabykina S, Bronstein I, Berezin V, Bock E, Lukanidin E (2000) Oligomeric forms of the metastasis-related Mts1 (S100A4) protein stimulate neuronal differentiation in cultures of rat hippocampal neurons. J Biol Chem 275: 41278-41286.
  • Rudland PS, Platt-Higgins A, Renshaw C, West CR, Winstanley JH, Robertson L, Barraclough R (2000) Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Cancer Res 60: 1595-1603.
  • Schmidt-Hansen B, Ornås D, Grigorian M, Klingelhöfer J, Tulchinsky E, Lukanidin E, Ambartsumian N (2004) Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23: 5487-5495.
  • Simpson PT, Shoker BS, Barraclough R, Halliwell N, Rudland PS, Sibson DR, Davies MP (2003) Examination of tumour histopathology and gene expression in a neu/S100A4 transgenic model of metastatic breast cancer. Int J Exp Pathol 84: 173-184.
  • Schmidt-Hansen B, Ornas D, Grigorian M, Klingelho J, Tulchinsky E, Lukanidin E, Ambartsumian N (2004) Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 23: 5487-5495.
  • Wang G, Platt-Higgins A, Carroll J, de Silva Rudland S, Winstanley J, Barraclough R, Rudland PS (2006) Induction of metastasis by S100P in a rat mammary model and its association with poor survival of breast cancer patients. Cancer Res 66: 1199-1207.
  • Zhang B, Cao X, Liu Y, Cao W, Zhang F, Zhang S, Li H, Ning L, Fu L, Niu Y, Niu R, Sun B, Hao X (2008) Tumor-derived matrix metalloproteinase-13 (MMP-13) correlates with poor prognoses of invasive breast cancer. BMC Cancer 8: 83–90.
Document Type
Publication order reference
Identifiers
YADDA identifier
bwmeta1.element.bwnjournal-article-abpv59p593kz
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