Skip to main content

Advertisement

SpringerLink
Log in

High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer

  • Research Article
  • Published:
Tumor Biology

Abstract

The transforming growth factor beta 1 (TGFB1) is a regulatory cytokine with both tumor suppressor and tumor-promoting effects in breast cancer (BC) cell lines and tissue. Data about level of circulating TGFB1 and its prognostic significance in BC patients is conflicting. The objective of this study is to determine the clinical significance of the serum TGFB1 levels in BC patients. We enrolled 96 female patients with histopathologically diagnosed BC who did not receive chemotherapy (CT) or radiotherapy. Serum TGFB1 levels were measured by ELISA method and compared with 30 healthy controls. The mean serum TGFB1 level of BC patients was significantly higher than controls (0.08 vs. 0.04 ng/ml, p < 0.001). There was no significant difference according to known disease-related clinicopathological or laboratory parameters. Serum TGFB1 level had a significant impact on overall survival in both univariate (p = 0.01) and multivariate analysis (p = 0.013). Serum TGFB1 level is elevated in BC patients and has a favorable prognostic value. However, it has no predictive role on CT response.

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

Fig. 1
Fig. 2
Fig. 3

Similar content being viewed by others

References

  1. Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127:2893–917.

    Article  CAS  PubMed  Google Scholar 

  2. Massague’ J. TGF b in cancer. Cell. 2008;134:215–30.

    Article  Google Scholar 

  3. Ilunga K, Nishiura R, Inada H, El-Karef A, Imanaka-Yoshida K, Sakakura T, et al. Co-stimulation of human breast cancer cells with transforming growth factor-beta and tenascin-C enhances matrix metalloproteinase-9 expression and cancer cell invasion. Int J Exp Pathol. 2004;85(6):373–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  4. Moses H, Barcellos-Hoff MH. TGF-beta biology in mammary development and breast cancer. Cold Spring Harb Perspect Biol. 2011;3(1):a003277.

    Article  PubMed Central  PubMed  Google Scholar 

  5. Maxwell CA, Fleisch MC, Costes SV, Erickson AC, Boissiere A, Gupta R, et al. Targeted and nontargeted effects of ionizing radiation that impact genomic instability. Cancer Res. 2008;68:8304–11.

    Article  CAS  PubMed  Google Scholar 

  6. Li B, Wen G, Zhao Y, Tong J, Hei TK. The role of TGFBI in mesothelioma and breast cancer: association with tumor suppression. BMC Cancer. 2012;12:239.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  7. Wen G, Partridge MA, Li B, Hong M, Liao W, Cheng SK, et al. TGFBI expression reduces in vitro and in vivo metastatic potential of lung and breast tumor cells. Cancer Lett. 2011;308(1):23–32.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  8. Forrester E, Chytil A, Bierie B, Aakre M, Gorska AE, Sharif-Afshar AR, et al. Effect of conditional knockout of the type II TGF-b receptor gene in mammary epithelia on mammary gland development and polyomavirus middle T antigen induced tumor formation and metastasis. Cancer Res. 2005;65:2296–302.

    Article  CAS  PubMed  Google Scholar 

  9. Yang L, Huang J, Ren X, Gorska AE, Chytil A, Aakre M, et al. Abrogation of TGF beta signaling in mammary carcinomas recruits Gr-1 + CD11b + myeloid cells that promote metastasis. Cancer Cell. 2008;13:23–35.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  10. Kong FM, Anscher MS, Murase T, Abbott BD, Iglehart JD, Jirtle RL. Elevated plasma transforming growth factor-beta 1 levels in breast cancer patients decrease after surgical removal of the tumor. Ann Surg. 1995;222(2):155–62.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  11. Hartmann MC, Dwyer RM, Costello M, Potter SM, Curran C, Hennessy E, et al. Relationship between CCL5 and transforming growth factor-β1 (TGFβ1) in breast cancer. Eur J Cancer. 2011;47(11):1669–75.

    Article  CAS  PubMed  Google Scholar 

  12. Gorsch SM, Memoli VA, Stukel TA, Gold LI, Arrick BA. Immunohistochemical staining for transforming growth factor beta 1 associates with disease progression in human breast cancer. Cancer Res. 1992;52(24):6949–52.

    CAS  PubMed  Google Scholar 

  13. Desruisseau S, Palmari J, Giusti C, Romain S, Martin PM, Berthois Y. Determination of TGF beta1 protein level in human primary breast cancers and its relationship with survival. Br J Cancer. 2006;94(2):239–46.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  14. Bao J, Wu ZS, Qi Y, Wu Q, Yang F. Expression of TGF-beta1 and the mechanism of invasiveness and metastasis induced by TGF-beta1 in breast cancer. Zhonghua Zhong Liu Za Zhi. 2009;31(9):679–82.

    CAS  PubMed  Google Scholar 

  15. Ya Y, Dukhanina O, Tang B, Mamura M, Letterio JJ, MacGregor J, et al. Lifetime exposure to a soluble TGF-{b} antagonist protects mice against metastasis without adverse side effects. J Clin Invest. 2002;109:1607–15.

    Article  Google Scholar 

  16. Gorska AE, Jensen RA, Shyr Y, Aakre ME, Bhowmick NA, Moses HL. Transgenic mice expressing a dominant- negative mutant type II transforming growth factor-b receptor exhibit impaired mammary development and enhanced mammary tumor formation. Am J Pathol. 2003;163:1539–49.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  17. Zhou YH, Liao SJ, Li D, Luo J, Wei JJ, Yan B, et al. TLR4 ligand/H2O2 enhances TGF-β1 signaling to induce metastatic potential of non-invasive breast cancer cells by activating non-Smad pathways. PLoS One. 2013;8(5):e65906.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. Moore LD, Isayeva T, Siegal GP, Ponnazhagan S. Silencing of transforming growth factor-beta1 in situ by RNA interference for breast cancer: implications for proliferation and migration in vitro and metastasis in vivo. Clin Cancer Res. 2008;14(15):4961–70.

    Article  CAS  PubMed  Google Scholar 

  19. Muraoka RS, Dumont N, Ritter CA, Dugger TC, Brantley DM, Chen J, et al. Blockade of TGF-beta inhibits mammary tumor cell viability, migration, and metastases. J Clin Invest. 2002;109(12):1551–9.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  20. Casey TM, Eneman J, Crocker A, White J, Tessitore J, Stanley M, et al. Cancer associated fibroblasts stimulated by transforming growth factor beta1 (TGF-beta 1) increase invasion rate of tumor cells: a population study. Breast Cancer Res Treat. 2008;110(1):39–49.

    Article  CAS  PubMed  Google Scholar 

  21. Sovak MA, Arsura M, Zanieski G, Kavanagh KT, Sonenshein GE. The inhibitory effects of transforming growth factor beta1 on breast cancer cell proliferation are mediated through regulation of aberrant nuclear factor-kappa B/Rel expression. Cell Growth Differ. 1999;10(8):537–44.

    CAS  PubMed  Google Scholar 

  22. Ito M, Minamiya Y, Kawai H, Saito S, Saito H, Nakagawa T, et al. Tumor-derived TGF beta-1 induces dendritic cell apoptosis in the sentinel lymph node. J Immunol. 2006;176(9):5637–43.

    Article  CAS  PubMed  Google Scholar 

  23. Wang Y, Lui WY. Transforming growth factor-β1 attenuates junctional adhesion molecule-A and contributes to breast cancer cell invasion. Eur J Cancer. 2012;48(18):3475–87.

    Article  CAS  PubMed  Google Scholar 

  24. Todorović-Raković N. TGF-beta 1 could be a missing link in the interplay between ER and HER-2 in breast cancer. Med Hypotheses. 2005;65(3):546–51.

    Article  PubMed  Google Scholar 

  25. Northey JJ, Dong Z, Ngan E, Kaplan A, Hardy WR, Pawson T, et al. Distinct phosphotyrosine-dependent functions of the ShcA adaptor protein are required for transforming growth factor β (TGFβ)-induced breast cancer cell migration, invasion, and metastasis. J Biol Chem. 2013;288(7):5210–122.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  26. Fynan TM, Reiss M. Resistance to inhibition of cell growth by transforming growth factor-b and its role in oncogenesis. Critical Rev Oncogen. 1993;4:493–540.

    CAS  Google Scholar 

  27. Ivanović V, Demajo M, Krtolica K, Krajnović M, Konstantinović M, Baltić V, et al. Elevated plasma TGF-beta1 levels correlate with decreased survival of metastatic breast cancer patients. Clin Chim Acta. 2006;371(1–2):191–3.

    Article  PubMed  Google Scholar 

  28. Kajdaniuk D, Marek B, Swietochowska E, Ostrowska Z, Glogowska-Szelag J, Kos-Kudla B, et al. Plasma transforming growth factor beta1 in breast cancer patients treated with CMF chemotherapy. J Clin Pharm Ther. 2000;25(4):291–4.

    Article  CAS  PubMed  Google Scholar 

  29. Panis C, Herrera AC, Victorino VJ, Aranome AM, Cecchini R. Screening of circulating TGF-β levels and its clinicopathological significance in human breast cancer. Anticancer Res. 2013;33(2):737–42.

    CAS  PubMed  Google Scholar 

  30. Wakefield LM, Letterio JJ, Chen T, Danielpour D, Allison RS, Pai LH, et al. Transforming growth factor-beta1 circulates in normal human plasma and is unchanged in advanced metastatic breast cancer. Clin Cancer Res. 1995;1(1):129–36.

    CAS  PubMed  Google Scholar 

  31. Sheen-Chen SM, Chen HS, Sheen CW, Eng HL, Chen WJ. Serum levels of transforming growth factor beta1 in patients with breast cancer. Arch Surg. 2001;136(8):937–40.

    Article  CAS  PubMed  Google Scholar 

  32. Chod J, Zavadova E, Halaska MJ, Strnad P, Fucikova T, Rob L. Preoperative transforming growth factor-beta 1 (TGF-beta 1) plasma levels in operable breast cancer patients. Eur J Gynaecol Oncol. 2008;29(6):613–6.

    CAS  PubMed  Google Scholar 

  33. Dave H, Shah M, Trivedi S, Shukla S. Prognostic utility of circulating transforming growth factor beta 1 in breast cancer patients. Int J Biol Markers. 2012;27(1):53–9.

    Article  CAS  PubMed  Google Scholar 

  34. Ivanović V, Todorović-Raković N, Demajo M, Nesković-Konstantinović Z, Subota V, Ivanisević-Milovanović O, et al. Elevated plasma levels of transforming growth factor-beta 1 (TGF-beta 1) in patients with advanced breast cancer: association with disease progression. Eur J Cancer. 2003;39(4):454–61.

    Article  PubMed  Google Scholar 

  35. Korantzis I, Kalogeras KT, Papaxoinis G, Kotoula V, Koutras A, Soupos N, et al. Expression of angiogenic markers in the peripheral blood of patients with advanced breast cancer treated with weekly docetaxel. Anticancer Res. 2012;32(10):4569–80.

    CAS  PubMed  Google Scholar 

  36. Duranyildiz D, Camlica H, Soydinc HO, Derin D, Yasasever V. Serum levels of angiogenic factors in early breast cancerremain close to normal. Breast. 2009;18(1):26–9.

    Article  PubMed  Google Scholar 

  37. Lebrecht A, Grimm C, Euller G, Ludwig E, Ulbrich E, Lantzsch T, et al. Transforming growth factor beta 1 serum levels in patients with preinvasive and invasive lesions of the breast. Int J Biol Markers. 2004;19(3):236–9.

    CAS  PubMed  Google Scholar 

  38. Todorović-Raković N, Nesković-Konstantinović Z, Nikolić-Vukosavljević D. Stage-related plasma values of transforming growth factor-beta1 are steroid receptors dependent. Clin Exp Med. 2009;9(4):313–7.

    Article  PubMed  Google Scholar 

  39. Grau AM, Wen W, Ramroopsingh DS, Gao YT, Zi J, Cai Q, et al. Circulating transforming growth factor-beta-1 and breast cancer prognosis: results from the Shanghai Breast Cancer Study. Breast Cancer Res Treat. 2008;112(2):335–41.

    Article  CAS  PubMed  Google Scholar 

  40. Papadopoulou E, Anagnostopoulos K, Tripsianis G, Tentes I, Kakolyris S, Galazios G, et al. Evaluation of predictive and prognostic significance of serum TGF-beta1 levels in breast cancer according to HER-2 codon 655 polymorphism. neoplasma. 2008;55(3):229–38.

    CAS  PubMed  Google Scholar 

Download references

Conflicts of interest

None

Author information

Authors and Affiliations

  1. Medical Oncology Department, Institute of Oncology, Istanbul University, Capa, Istanbul, Turkey

    Rumeysa Ciftci, Faruk Tas, Senem Karabulut, Fatma Sen, Serkan Keskin, Leyla Kilic, İbrahim Yildiz, Hamza Ugur Bozbey & Sezai Vatansever

  2. Basic Oncology Department, Institute of Oncology, Istanbul University, Capa, Istanbul, Turkey

    Ceren Tilgen Yasasever, Ece Aksit & Derya Duranyildiz

Authors
  1. Rumeysa Ciftci
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Faruk Tas
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ceren Tilgen Yasasever
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ece Aksit
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Senem Karabulut
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Fatma Sen
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Serkan Keskin
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Leyla Kilic
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. İbrahim Yildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Hamza Ugur Bozbey
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Derya Duranyildiz
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Sezai Vatansever
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rumeysa Ciftci.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Ciftci, R., Tas, F., Yasasever, C.T. et al. High serum transforming growth factor beta 1 (TGFB1) level predicts better survival in breast cancer. Tumor Biol. 35, 6941–6948 (2014). https://doi.org/10.1007/s13277-014-1932-y

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s13277-014-1932-y

Keywords

Search

Navigation