Tumor Biology

Research Article

Different Expression and Clinical Role of S100A4 in Serous Ovarian Carcinoma at Different Anatomic Sites

Mælandsmo G.M.a · Flørenes V.A.b · Nguyen M.T.P.b · Flatmark K.a · Davidson B.b, c

Author affiliations

Departments of aTumor Biology and Surgery and bPathology, Norwegian Radium Hospital, Rikshospitalet University Hospital, and cFaculty of Medicine, University of Oslo, Oslo, Norway

Keywords: EffusionsOvarian carcinomaS100A4Survival analysis

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Tumor Biol 2009;30:15–25
https://doi.org/10.1159/000199447

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Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: August 20, 2008
Accepted: December 03, 2008
Published online: February 05, 2009
Issue release date: April 2009

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 3

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: https://www.karger.com/TBI

Abstract

The present study analyzed the site-specific expression and clinical role of S100A4 in advanced-stage ovarian carcinoma (OC). S100A4 expression was analyzed in 161 effusions, 67 primary carcinomas and 127 solid metastases using immunohistochemistry. S100A4 levels were additionally measured in 20 effusion supernatants using the immunofluorometric assay IFMA. Cytoplasmic and nuclear S100A4 was detected in cancer cells at all anatomic sites, while myofibroblasts in solid tumors expressed only cytoplasmic S100A4. Nuclear expression was higher in solid tumors than in effusions (p < 0.001), while stromal cell expression was higher in metastases than primary tumors (p = 0.001). IFMA analysis detected S100A4 in all 20 supernatants. Nuclear S100A4 expression in primary carcinomas (p = 0.049), FIGO stage IV (p = 0.019) and poor response to chemotherapy at diagnosis (p < 0.001) were associated with worse overall survival. All three parameters were independent prognosticators in Cox analysis (S100A4: p = 0.048, FIGO stage: p = 0.015, response to chemotherapy: p < 0.001). S100A4 is frequently expressed in tumor and host cells in OC, with upregulated stromal expression in solid metastases. Tumor cell nuclear S100A4 expression is higher in solid tumors than in effusions, and is associated with more aggressive clinical disease in primary carcinoma, suggesting that the tumor-promoting role of this molecule is predominantly exerted at this anatomic site.

© 2009 S. Karger AG, Basel



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References

  1. Jemal A, Siegel R, Ward E, Murray T, Xu J, Thun MJ: Cancer statistics, 2007. CA Cancer J Clin 2007;57:43–66.
    External Resources
  2. Davidson B, Risberg R, Reich R, Berner A: Effusion cytology in ovarian cancer – new molecular methods as aids to diagnosis and prognosis. Clin Lab Med 2003;23:729–754.
    External Resources
  3. Davidson B: Malignant effusions – from diagnosis to biology: Diagn Cytopathol 2004;31:246–254.
  4. Donato R: Intracellular and extracellular roles of S100 proteins. Microsc Res Tech 2003;60:540–551.
    External Resources
  5. Ambartsumian NS, Grigorian MS, Larsen IF, et al: Metastasis of mammary carcinomas in GRS/A hybrid mice transgenic for the mts1 gene. Oncogene 1996;13:1621–1630.
    External Resources
  6. Davies MP, Rudland PS, Robertson L, Parry EW, Jolicoeur P, Barraclough R: Expression of the calcium-binding protein S100A4 (p9Ka) in MMTV-neu transgenic mice induces metastasis of mammary tumours. Oncogene 1996;13:1631–1637.
    External Resources
  7. Grigorian M, Ambartsumian N, Lykkesfeldt AE, et al: Effect of mts1 (S100A4) expression on the progression of human breast cancer cells. Int J Cancer 1996;67:831–841.
    External Resources
  8. Mælandsmo GM, Hovig E, Skrede M, et al: Reversal of the in vivo metastatic phenotype of human tumor cells by an anti-CAPL (mts1) ribozyme. Cancer Res 1996;56:5490–5498.
    External Resources
  9. Takenaga K, Nakamura Y, Sakiyama S: Expression of antisense RNA to S100A4 gene encoding an S100-related calcium-binding protein suppresses metastatic potential of high-metastatic Lewis lung carcinoma cells. Oncogene 1997;14:331–337.
    External Resources
  10. Garrett SC, Varney KM, Weber DJ, Bresnick AR: S100A4, a mediator of metastasis. J Biol Chem 2006;281:677–680.
    External Resources
  11. Ford HL, Zain SB: Interaction of metastasis associated Mts1 protein with nonmuscle myosin. Oncogene 1995;10:1597–1605.
    External Resources
  12. Kriajevska M, Bronstein IB, Scott DJ, et al: Metastasis-associated protein Mts1 (S100A4) inhibits CK2-mediated phosphorylation and self-assembly of the heavy chain of nonmuscle myosin. Biochim Biophys Acta 2000;1498:252–263.
    External Resources
  13. Li ZH, Bresnick AR: The S100A4 metastasis factor regulates cellular motility via a direct interaction with myosin-IIA. Cancer Res 2006;66:5173–5180.
    External Resources
  14. Saleem M, Kweon MH, Johnson JJ, et al: S100A4 accelerates tumorigenesis and invasion of human prostate cancer through the transcriptional regulation of matrix metalloproteinase 9. Proc Natl Acad Sci USA 2006;103:14825–14830.
    External Resources
  15. Bjørnland K, Winberg JO, Odegaard OT, et al: S100A4 involvement in metastasis: deregulation of matrix metalloproteinases and tissue inhibitors of matrix metalloproteinases in osteosarcoma cells transfected with an anti-S100A4 ribozyme. Cancer Res 1999;59:4702–4708.
    External Resources
  16. Schmidt-Hansen B, Ornås D, Grigorian M, et al: Extracellular S100A4(mts1) stimulates invasive growth of mouse endothelial cells and modulates MMP-13 matrix metalloproteinase activity. Oncogene 2004;23:5487–5495.
    External Resources
  17. Flatmark K, Pedersen KB, Nesland JM, et al: Nuclear localization of the metastasis-related protein S100A4 correlates with tumour stage in colorectal cancer. J Pathol 2003;200:589–595.
    External Resources
  18. Cabezón T, Celis JE, Skibshøj I, et al: Expression of S100A4 by a variety of cell types present in the tumor microenvironment of human breast cancer. Int J Cancer 2007;121:1433–1444.
    External Resources
  19. Schmidt-Hansen B, Klingelhöfer J, Grum-Schwensen B, et al: Functional significance of metastasis-inducing S100A4(Mts1) in tumor-stroma interplay. J Biol Chem 2004;279:24498–24504.
    External Resources
  20. Grigorian M, Andresen S, Tulchinsky E, et al: Tumor suppressor p53 protein is a new target for the metastasis-associated Mts1/S100A4 protein: functional consequences of their interaction. J Biol Chem 2001;276:22699–22708.
    External Resources
  21. Semov A, Moreno MJ, Onichtchenko A, et al: Metastasis-associated protein S100A4 induces angiogenesis through interaction with Annexin II and accelerated plasmin formation. J Biol Chem 2005;280:20833–20841.
    External Resources
  22. Rudland PS, Platt-Higgins A, Renshaw C, et al: Prognostic significance of the metastasis-inducing protein S100A4 (p9Ka) in human breast cancer. Cancer Res 2000;60:1595–1603.
    External Resources
  23. Gongoll S, Peters G, Mengel M, et al: Prognostic significance of calcium-binding protein S100A4 in colorectal cancer. Gastroenterology 2002;123:1478–1484.
    External Resources
  24. Davies BR, O’Donnell M, Durkan GC, et al: Expression of S100A4 protein is associated with metastasis and reduced survival in human bladder cancer. J Pathol 2002;196:292–299.
    External Resources
  25. Kimura K, Endo Y, Yonemura Y, et al: Clinical significance of S100A4 and E-cadherin-related adhesion molecules in non-small cell lung cancer. Int J Oncol 2000;16:1125–1131.
    External Resources
  26. Kikuchi N, Horiuchi A, Osada R, et al: Nuclear expression of S100A4 is associated with aggressive behavior of epithelial ovarian carcinoma: an important autocrine/paracrine factor in tumor progression. Cancer Sci 2006;97:1061–1069.
    External Resources
  27. Davidson B, Nielsen S, Christensen J, Asschenfeldt P, Berner A, Risberg B, Johansen P: The role of desmin and N-cadherin in effusion cytology: a comparative study using established markers of mesothelial and epithelial cells. Am J Surg Pathol 2001;25:1405–1412.
    External Resources
  28. Flatmark K, Maelandsmo GM, Mikalsen SO, Nustad K, Varaas T, Rasmussen H, Meling GI, Fodstad Ø, Paus E: Immunofluorometric assay for the metastasis-related protein S100A4: release of S100A4 from normal blood cells prohibits the use of S100A4 as a tumor marker in plasma and serum. Tumor Biol 2004;25:31–40.
    External Resources
  29. Andersen K, Nesland JM, Holm R, Flørenes VA, Fodstad Ø, Maelandsmo GM: Expression of S100A4 combined with reduced E-cadherin expression predicts patient outcome in malignant melanoma. Mod Pathol 2004;17:990–997.
    External Resources
  30. Davidson B, Reich R, Berner A, Givant-Horwitz V, Goldberg I, Risberg B, Kristensen GB, Tropé CG, Bryne M, Kopolovic J, Nesland JM: Ovarian carcinoma cells in serous effusions show altered MMP-2 and TIMP-2 mRNA levels. Eur J Cancer 2001;37:2040–2049.
    External Resources
  31. Davidson B, Goldberg I, Berner A, Kristensen GB, Reich R: EMMPRIN (extracellular matrix metalloproteinase inducer) is a novel marker of poor outcome in serous ovarian carcinoma. Clin Exp Metastasis 2003;20:161–169.
    External Resources
  32. Sivertsen S, Berner A, Michael CW, Bedrossian C, Davidson B: Cadherin expression in ovarian carcinoma and malignant mesothelioma cell effusions. Acta Cytol 2006;50:603–607.
    External Resources
  33. Davidson B, Berner A, Nesland JM, Risberg B, Berner HS, Tropé CG, Kristensen GB, Bryne M, Flørenes VA: E-cadherin and α-, β- and γ-catenin protein expression is up-regulated in ovarian carcinoma cells in serous effusions. J Pathol 2000;192:460–469.
    External Resources
  34. Davidson B, Reich R, Kopolovic J, Berner A, Nesland JM, Kristensen GB, Tropé CG, Bryne M, Risberg B, van de Putte G, Goldberg I: Interleukin-8 and vascular endothelial growth factor mRNA levels are down-regulated in ovarian carcinoma cells in serous effusions. Clin Exp Metastasis 2002;19:135–144.
    External Resources
  35. Davidson B, Reich R, Lazarovici P, Nesland JM, Risberg B, Tropé CG, Flørenes VA: Expression and activation of the nerve growth factor receptor TrkA in serous ovarian carcinoma. Clin Cancer Res 2003;9:2248–2259.
    External Resources
  36. Givant-Horwitz V, Davidson B, Lazarovici P, Schaefer E, Nesland JM, Tropé CG, Reich R: Mitogen-activated protein kinases (MAPK) as predictors of clinical outcome in serous ovarian carcinoma in effusions. Gynecol Oncol 2003;91:160–172.
    External Resources
  37. Davidson B, Hadar R, Schlossberg A, Sternlicht T, Slipicevic A, Skrede M, Risberg B, Flørenes VA, Kopolovic J, Reich R: Expression and clinical role of DJ-1, a negative regulator of PTEN, in ovarian carcinoma. Hum Pathol 2008;39:87–95.
    External Resources
  38. Lee WY, Su WC, Lin PW, Guo HR, Chang TW, Chen HH: Expression of S100A4 and Met: potential predictors for metastasis and survival in early-stage breast cancer. Oncology 2004;66:429–438.
    External Resources
  39. Pedersen KB, Nesland JM, Fodstad Ø, Mælandsmo GM: Expression of S100A4, E-cadherin, α- and β-catenin in breast cancer biopsies. Br J Cancer 2002;87:1281–1286.
    External Resources
  40. Schneider M, Hansen JL, Sheikh SP: S100A4: a common mediator of epithelial-mesenchymal transition, fibrosis and regeneration in disease? J Mol Med 2008;86:507–522.
    External Resources
  41. Kohya N, Kitajima Y, Jiao W, Miyazaki K: Effects of E-cadherin transfection on gene expression of a gallbladder carcinoma cell line: repression of MTS1/S100A4 gene expression. Int J Cancer 2003;104:44–53.
    External Resources
  42. Elloul S, Silins I, Tropé CG, Benshushan A, Davidson B, Reich R: Expression of E-cadherin transcriptional regulators in ovarian carcinoma. Virchows Arch 2006;449:520–528.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Research Article

Received: August 20, 2008
Accepted: December 03, 2008
Published online: February 05, 2009
Issue release date: April 2009

Number of Print Pages: 11
Number of Figures: 2
Number of Tables: 3

ISSN: 1010-4283 (Print)
eISSN: 1423-0380 (Online)

For additional information: https://www.karger.com/TBI

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