Skip to main content

Advertisement

SpringerLink
Log in

Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype

  • Preclinical study
  • Published:
Breast Cancer Research and Treatment Aims and scope Submit manuscript

Summary

Members of the syndecan and glypican families of cell surface heparan sulfate proteoglycans (HSPGs) are modulators of growth factor signaling and cell adhesion. Both loss and gain in expression of syndecans and glypicans has been associated with malignant progression. The goal of this project was to investigate a possible relationship between expression of cell surface HSPGs (syndecan-1, syndecan-4 and glypican-1) and established prognostic factors or clinical outcome in breast carcinomas. Tissue arrays containing 207 human breast carcinoma samples in duplicate were immuno-labeled with antibodies to syndecan-1, syndecan-4, glypican-1, Ki67, E-cadherin, estrogen receptor (ER) and progesterone receptor (PR). Clinical follow-up information was available for up to 18.6 years (median follow-up 6.2 years). Syndecan-1 and syndecan-4 expression in carcinoma cells ranged from complete loss to high expression, but glypican-1 was detected only in a small subset of breast carcinomas. Expression of all three HSPGs was significantly associated with the Ki67 proliferation index (syndecan-1: p=0.0025; syndecan-4: p<0.0001; glypican-1 p=0.01). Syndecan-1 and syndecan-4 expression correlated with ER negativity, grade, and size of the primary tumors. Syndecan-1 expression (but not syndecan-4 nor glypican-1) predicted patient outcome (DFS: p=0.0054; OS: p=0.0086). However, multivariate analysis failed to identify syndecan-1 as an independent prognostic marker, which was due to its significant association with established prognostic factors. The strong association between cell surface HSPGs and the Ki67 proliferation marker would support a biologic role in carcinoma growth regulation. Furthermore, the close correlation between syndecan expression and negative ER status raises the possibility of hormonal regulation or more likely an association with an aggressive, ER-negative carcinoma phenotype.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Barbareschi M, Maisonneuve P, Aldovini D, et al., 2003; High syndecan-1 expression in breast carcinoma is related to an aggressive phenotype and to poorer prognosis Cancer 98:474–483

    Article  PubMed  Google Scholar 

  2. Leivonen M, Lundin J, Nordling S, et al., 2004; Prognostic value of syndecan-1 expression in breast cancer Oncology 67:11–18

    Article  PubMed  CAS  Google Scholar 

  3. Kleeff J, Ishiwata T, Kumbasar A, et al., 1998; The cell-surface heparan sulfate proteoglycan glypican-1 regulates growth factor action in pancreatic carcinoma cells and is overexpressed in human pancreatic cancer J Clin Invest 102:1662–1673

    Article  PubMed  CAS  Google Scholar 

  4. Matsuda K, Maruyama H, Guo F, et al., 2001; Glypican-1 is overexpressed in human breast cancer and modulates the mitogenic effects of multiple heparin-binding growth factors in breast cancer cells Cancer Res 61:5562–5569

    PubMed  CAS  Google Scholar 

  5. Guimond SE, Turnbull JE, 1999; Fibroblast growth factor receptor signalling is dictated by specific heparan sulphate saccharides Curr Biol 9:1343–1346

    Article  PubMed  CAS  Google Scholar 

  6. Schlessinger J, Plotnikov AN, Ibrahimi OA, et al., 2000; Crystal structure of a ternary FGF-FGFR-heparin complex reveals a dual role for heparin in FGFR binding and dimerization Mol Cell 6:743–750

    Article  PubMed  CAS  Google Scholar 

  7. Mundhenke C, Meyer K, Drew S, et al., 2002; Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 receptor binding in breast carcinomas Am J Pathol 160:185–194

    PubMed  CAS  Google Scholar 

  8. Beauvais DM, Burbach BJ, Rapraeger AC, 2004; The syndecan-1 ectodomain regulates alphavbeta3 integrin activity in human mammary carcinoma cells J Cell Biol 167:171–181

    Article  PubMed  CAS  Google Scholar 

  9. Burbach BJ, Ji Y, Rapraeger AC, 2004; Syndecan-1 ectodomain regulates matrix-dependent signaling in human breast carcinoma cells Exp Cell Res 300:234–247

    Article  PubMed  CAS  Google Scholar 

  10. Wolberg WH, Street WN, 2002; Computer-generated nuclear features compared with axillary lymph node status and tumor size as indicators of breast cancer survival Hum Pathol 33:1086–1091

    Article  PubMed  Google Scholar 

  11. Dalton LW, Pinder SE, Elston CE, et al., 2000; Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement Mod Pathol 13:730–735

    Article  PubMed  CAS  Google Scholar 

  12. Qiao D, Meyer K, Mundhenke C, et al., 2003; Heparan sulfate proteoglycans as regulators of fibroblast growth factor-2 signaling in brain endothelial cells. Specific role for glypican-1 in glioma angiogenesis J Biol Chem 278:16045–16053

    Article  PubMed  CAS  Google Scholar 

  13. David G, Bai XM, Van der Schueren B, et al., 1992; Developmental changes in heparan sulfate expression: in situ detection with mAbs J Cell Biol 119:961–975

    Article  PubMed  CAS  Google Scholar 

  14. David G, Lories V, Decock B, et al., 1990; Molecular cloning of a phosphatidylinositol-anchored membrane heparan sulfate proteoglycan from human lung fibroblasts J Cell Biol 111:3165–3176

    Article  PubMed  CAS  Google Scholar 

  15. Harvey JM, Clark GM, Osborne CK, et al., 1999; Estrogen receptor status by immunohistochemistry is superior to the ligand-binding assay for predicting response to adjuvant endocrine therapy in breast cancer J Clin Oncol 17:1474–1481

    PubMed  CAS  Google Scholar 

  16. Burbach BJ, Friedl A, Mundhenke C, et al., 2003; Syndecan-1 accumulates in lysosomes of poorly differentiated breast carcinoma cells Matrix Biol 22:163–177

    Article  PubMed  CAS  Google Scholar 

  17. Kato M, Saunders S, Nguyen H, et al., 1995; Loss of cell surface syndecan-1 causes epithelia to transform into anchorage-independent mesenchyme-like cells Mol Biol Cell 6:559–576

    PubMed  CAS  Google Scholar 

  18. Leppa S, Vleminckx K, Van Roy F, et al., 1996; Syndecan-1 expression in mammary epithelial tumor cells is E-cadherin-dependent J Cell Sci 109(Pt 6):1393–1403

    PubMed  CAS  Google Scholar 

  19. Rasbridge SA, Gillett CE, Sampson SA, et al., 1993; Epithelial (E-) and placental (P-) cadherin cell adhesion molecule expression in breast carcinoma J Pathol 169:245–250

    Article  PubMed  CAS  Google Scholar 

  20. Zhao H, Langerod A, Ji Y, et al., 2004; Different gene expression patterns in invasive lobular and ductal carcinomas of the breast Mol Biol Cell 15:2523–2536

    Article  PubMed  CAS  Google Scholar 

  21. Filmus J, 2001; Glypicans in growth control and cancer Glycobiology 11:19R–23R

    Article  PubMed  CAS  Google Scholar 

  22. Zellweger T, Ninck C, Mirlacher M, et al., 2003; Tissue microarray analysis reveals prognostic significance of syndecan-1 expression in prostate cancer Prostate 55:20–29

    Article  PubMed  Google Scholar 

  23. Zellweger T, Ninck C, Bloch M, et al., 2005; Expression patterns of potential therapeutic targets in prostate cancer Int J Cancer 113:619–628

    Article  PubMed  CAS  Google Scholar 

  24. Alexander CM, Reichsman F, Hinkes MT, et al., 2000; Syndecan-1 is required for Wnt-1-induced mammary tumorigenesis in mice Nat Genet 25:329–332

    Article  PubMed  CAS  Google Scholar 

  25. Woods A, Couchman JR, 2001; Syndecan-4 and focal adhesion function Curr Opin Cell Biol 13:578–583

    Article  PubMed  CAS  Google Scholar 

  26. Beauvais DM, Rapraeger AC, 2003; Syndecan-1-mediated cell spreading requires signaling by alphavbeta3 integrins in human breast carcinoma cells Exp Cell Res 286:219–232

    Article  PubMed  CAS  Google Scholar 

  27. Jaakkola P, Maatta A, Jalkanen M, 1998; The activation and composition of FiRE (an FGF-inducible response element) differ in a cell type- and growth factor-specific manner Oncogene 17:1279–1286

    Article  PubMed  CAS  Google Scholar 

  28. Maatta A, Jaakkola P, Jalkanen M, 1999; Extracellular matrix-dependent activation of syndecan-1 expression in keratinocyte growth factor-treated keratinocytes J Biol Chem 274:9891–9898

    Article  PubMed  CAS  Google Scholar 

  29. Porter D, Lahti-Domenici J, Keshaviah A, et al., 2003; Molecular markers in ductal carcinoma in situ of the breast Mol Cancer Res 1:362–375

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

Satoshi Kinoshita is acknowledged for his technical assistance in producing the tissue arrays and Sally Drew for performing the immunohistochemical stains. We also thank Dr. Caroline Alexander for helpful discussions. This work was in part funded by grants from the Susan G. Komen Foundation (BCTR0402969) and the␣National institutes of Health (R01-CA107012). The funding sources did not influence the study design. The departmental translational research initiative in pathology (TRIP lab) also contributed to this study.

Author information

Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, University of Wisconsin-Madison, Madison, WI, USA

    Füsun Baba, Kathryn Swartz, Regina van Buren, Yong Zhang & Andreas Friedl

  2. Department of Biostatistics and Medical Informatics, University of Wisconsin-Madison, Madison, WI, USA

    Jens Eickhoff

  3. Department of Surgery, University of Wisconsin-Madison, Madison, WI, USA

    William Wolberg

  4. School of Medicine, Harran University, Sanliurfa, Turkey

    Füsun Baba

Authors
  1. Füsun Baba
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Kathryn Swartz
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Regina van Buren
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jens Eickhoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Yong Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. William Wolberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Andreas Friedl
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Andreas Friedl.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Baba, F., Swartz, K., van Buren, R. et al. Syndecan-1 and syndecan-4 are overexpressed in an estrogen receptor-negative, highly proliferative breast carcinoma subtype. Breast Cancer Res Treat 98, 91–98 (2006). https://doi.org/10.1007/s10549-005-9135-2

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10549-005-9135-2

Keywords

Search

Navigation