Skip to main content

Advertisement

Log in

Expression of transforming growth factor β in renal cell carcinoma and matched non-involved renal tissue

  • Original Paper
  • Published:
Urological Research Aims and scope Submit manuscript

Abstract

TGFβ1 is one of several cytokines produced by proximal tubular and renal cancer cells. Previous studies have been mainly focused on determining plasma or serum TGFβ levels, its effect on RCC cultures, and the expression of TGFβ mRNA. Cancerous and autologous normal kidney samples were obtained from 24 patients treated by radical nephrectomy. TGFβ1 expression was determined using a semi quantitative Western blot analysis and immunohistochemistry. Blot densities and immunohistochemical expression intensities in normal and neoplastic tissue were compared, and subsequently correlated to tumor stage, histological type and nuclear grade. All tissue samples examined expressed TGFβ1; mean tumor to non-involved kidney spot density ratio correlated with advancing stage and higher nuclear grade. The overexpression of TGFβ1 in certain RCCs may partially explain their resistance to the growth suppression action of TGFβ. The correlation with tumor stage and grade indicates a possible role in the development of metastatic potential as well as in host’s immune response modulation.

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

Access this article

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

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Atlas I, Mendelsohn J, Baselga J, Fair WR, Masui H, Kumar R (1992) Growth regulation of human renal carcinoma cells: role of transforming growth factor alpha. Cancer Res 52:3335

    CAS  PubMed  Google Scholar 

  2. Border W, Noble N (1995) Targeting TGFβ for treatment of diseases. Nat Med 1:1000

    CAS  PubMed  Google Scholar 

  3. Cardillo MR, Lazzereschi D, Galdini O, Di Silverio F, Colletta G (2001) Transforming growth factor-beta pathway in human renal cell carcinoma and surrounding normal-appearing renal parenchyma. Anal Quant Cytol Histol 23:109

    CAS  PubMed  Google Scholar 

  4. Cerwenka A, Bevec D, Majdic O, Knapp W, Holter W (1994) TGF-beta 1 is a potent inducer of human effector T cells. J Immunol 153:4367

    CAS  PubMed  Google Scholar 

  5. Chang SG, Shin C, Rho SK, Kim DK, Kim JH (1998) Cytokine production in primary histoculture by human normal kidney, renal cell carcinoma and benign renal angiomyolipoma tissues. Anticancer Res 18:4195

    CAS  PubMed  Google Scholar 

  6. Derynck R, Goeddel DV, Ullrich A, Gutterman JU, Wiiliams RD, Bringman TS, Berger WH (1987) Synthesis of messenger RNAs for transforming growth factors α and β and the epidermal growth factor receptors by human tumors. Cancer Res 47:707

    CAS  PubMed  Google Scholar 

  7. Filmus J, Kerbel RS (1993) Development of resistance mechanisms to the growth-inhibitory effects of transforming growth factor-beta during tumor progression. Curr Opin Oncol 5:123

    CAS  PubMed  Google Scholar 

  8. Gomella LG, Sargent ER, Linehan WM, Kasid A (1989) Transforming growth factor-beta inhibits the growth of renal cell carcinoma in vitro. J Urol 141:1240

    Google Scholar 

  9. Gomella LG, Sargent ER, Wade TP, Anglard P, Linehan WM, Kasid A (1989) Expression of transforming growth factor α in normal human adult kidney and of transforming growth factors α and β1 in renal cell carcinoma. Cancer Res 49:6972

    CAS  PubMed  Google Scholar 

  10. Hall S, Hsieh T-C, Ng C-Y, Mallouh C, Wu JM (1996) Control of renal carcinoma TC-1 growth, cyclin/kinase and nm23 expression by IFN-γ and TGF-β. Anticancer Res 16:1755

    CAS  PubMed  Google Scholar 

  11. Hegele A, Vagra Z, Von Knobloch R, Heidenreich A, Kropf J, Hofmann R (2002) TGFβ1 in patients with renal cell carcinoma. Urol Res 30:126

    Article  CAS  PubMed  Google Scholar 

  12. Herman ME, Katzenellenbogen BS (1994) Alterations in transforming growth factor α and β production and cell responsiveness during the progression of MCF-7 human breast cancer cells to eostrogen–autonomous growth. Cancer Res 54:5876

    Google Scholar 

  13. Junker U, Knoefel B, Rebstock K, Steiner T, Wunderlich H, Junker K, Reinhold D (1996) Transforming growth factor beta 1 is significantly elevated in plasma of patients suffering from renal cell carcinoma. Cytokine 8:794

    Article  CAS  PubMed  Google Scholar 

  14. Junker U, Haufe CC, Nuske K, Rebstock K, Steiner T, Wunderlich H, Junker K, Reinhold D (2000) Elevated plasma TGFbeta1 in renal diseases: cause or consequence ? Cytokine 12:1084

    Article  CAS  PubMed  Google Scholar 

  15. Kerbel RS (1992) Expression of multi-cytokine resistance and multi-growth factor independence in advanced stage metastatic cancer. Malignant melanoma as a paradigm. Am J Pathol 141:519

    CAS  PubMed  Google Scholar 

  16. Knoefel B, Nuske K, Steiner T, Junker K, Kosmehl H, Rebstock K, Reinhold D, Junker U (1997) Renal cell carcinomas produce IL-6, IL-10, IL-11 and TGF beta-1 in primary cultures and modulate T-lymphocyte blast formation. J Interferon Cytokine Res 17:95

    CAS  PubMed  Google Scholar 

  17. Kundu SD, Kim IY, Zelner D, Janulis L, Goodwin S, Engel JD, Lee C (1998) Absence of expression of transforming growth factor-beta type II receptor is associated with an aggressive growth pattern in a murine renal cell carcinoma cell line, Renca. J Urol 160:1883

    Google Scholar 

  18. Laemli UK (1970) Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680

    PubMed  Google Scholar 

  19. Landis SH, Murray T, Bolden S, Wingo PA (1999) Cancer statistics 1999. CA Cancer J Clin 49:8

    CAS  PubMed  Google Scholar 

  20. Lyons RM, Moses HL (1990) Transforming growth factors and the regulation of cell proliferation. Eur J Biochem 187:467

    CAS  PubMed  Google Scholar 

  21. Maniatis T, Fritch EF and Sambrook KJ (1982) Detection and Analysis of proteins expressed from cloned genes. In: Maniatis T, Fritch EF, Sambrook KJ (eds) Molecular cloning: a laboratory manual. Cold Spring Harbor, New York, p 18.47

  22. Maniatis T, Fritsch EF, Sambrook KJ (1982) Detection and analysis of proteins expressed from cloned genes. In: Maniatis T, Fritch EF, Sambrook KJ (eds) Molecular cloning: a laboratory manual. Cold Spring Harbor, New York, p 18.60

  23. Markowitz SD, Roberts AB (1996) Tumor suppressor activity of the TGFβ pathway in human cancers. Cytokine Growth Factor Rev 7:93

    Article  CAS  PubMed  Google Scholar 

  24. Massague J (1990) The transforming growth factor β family. Annu Rev Cell Biol 6:597

    CAS  PubMed  Google Scholar 

  25. Michel K, Tso CL, Mulders P, Kernion JD, Beldegrun A (1997) Expression of TGFβ1 in renal cell carcinoma (RCC); putative role of TGFβ as tumor infiltrating lymphocyte (TIL) suppressor. J Urol 157 [Suppl]:376

  26. Miyazono K, Ichijo H and Heldin CH (1993) Transforming growth factor β: Latent forms, binding proteins and receptors. Growth Factors 8:11

    CAS  PubMed  Google Scholar 

  27. Mulder KM, Ramey MR, Hoosen NM, Levine AE, Hinshaw XH, Brattain DE, Brattain MG (1988) Characterization of transforming growth factor-beta-resistant subclones isolated from a transforming growth factor-beta-sensitive human colon carcinoma cell line. Cancer Res 48:7120

    CAS  PubMed  Google Scholar 

  28. Olive C, Cheung C, Nicol D, Falk MC (1998) Expression of cytokine mRNA transcripts in renal cell carcinoma. Immunol Cell Biol 76:357

    Article  CAS  PubMed  Google Scholar 

  29. Phillips AO, Steadman R, Topley N, Williams JD (1995) Elevated D-glucose concentrations modulate TGF-beta1 synthesis by human cultured renal proximal tubular cells .The permissive role of platelet-derived growth factor. Am J Pathol 147:362

    CAS  PubMed  Google Scholar 

  30. Polyak K (1996) Negative regulation of cell growth by TGF beta. Biochim Biophys Acta 1242:185

    Article  CAS  PubMed  Google Scholar 

  31. Ramp U, Jaquet K, Reinecke P, Nitsch T, Gabbert HE, Gerharz CD (1997) Acquisition of TGF-beta 1 resistance: an important progression factor in human renal cell carcinoma. Lab Invest 76:739

    CAS  PubMed  Google Scholar 

  32. Roberts AB, Sporn MB, Assoian RK, Smith JM, Roche WS, Wakefield LA, Heine UI, Liotta LA, Falanga V, Kehl JH, Fauci AS (1986) Transforming growth factor β: rapid induction of fibrosis and angiogenesis in vivo and stimulation of collagen formation in vitro. Proc Natl Acad Sci U S A 83:4167

    CAS  PubMed  Google Scholar 

  33. Sankar S, Mahooti–Brooks N, Bensen L, McCarthy TL, Centrella M, Madri JA (1996) Modulation of transforming growth factor beta receptor levels on microvascular endothelial cells during in vitro angiogenesis. J Clin Invest 97:1436

    CAS  PubMed  Google Scholar 

  34. Sene AP, Hunt L, McMahon RF, Carroll RN (1992) Renal carcinoma in patients undergoing nephrectomy: analysis of survival and prognostic factors. Br J Urol 70:125

    CAS  PubMed  Google Scholar 

  35. Smith PK, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano MD, Fujimoto EK, Gocke NM, Olson BJ, Klenk DC (1985) Measurement of protein using bicinchoninic acid. Anal Biochem 150:76

    CAS  PubMed  Google Scholar 

  36. Storkel S, Eble J, Adlakha K, Amin M, Blute ML, Bostwick DG, Darson M, Delahunt B, Iczkowski K (1997) Classification of renal cell carcinoma: Workgroup No1, Union Internationale Contre le Cancer (UICC) and the American Joint Committee on Cancer (AJCC). Cancer 80:987

    Article  CAS  PubMed  Google Scholar 

  37. Towbin H, Staehelin T, Gordon J (1979) Electrophoretic transfer of proteins from polyacrylamide gels to nitrocellulose sheets: procedure and some applications. Proc Natl Acad Sci U S A 76:4350

    CAS  PubMed  Google Scholar 

  38. Van Brussel JP, Mickisch GH (1999) Prognostic factors in renal cell and bladder cancer. BJU Int 83:902

    Article  PubMed  Google Scholar 

  39. Wechsel HW, Bichler KH, Feil G, Loeser W, Lahme S, Petri E (1999) Renal cell carcinoma: relevance of angiogenetic factors. Anticancer Res 19:1537

    CAS  PubMed  Google Scholar 

  40. Wunderlich H, Steiner T, Junker U, Knoefel B, Schlichter A, Schubert J (1996) Serum transforming growth factor β1 in patients with renal cell carcinoma. J Urol 157:1602

    Google Scholar 

  41. Wunderlich H, Steiner T, Kosmehl H, Junker U, Reinhold D, Reichelt O, Zermann DH, Schubert J (1998) Increased transforming growth factor beta 1 plasma level in patients with renal cell carcinoma: a tumor-specific marker? Urol Int 60:205

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors acknowledge the skillful technical contribution of Penelope Chiara (medical arts), Despina Karandrea and Vasiliki Dotsika.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Dionisios Mitropoulos.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mitropoulos, D., Kiroudi, A., Christelli, E. et al. Expression of transforming growth factor β in renal cell carcinoma and matched non-involved renal tissue. Urol Res 32, 317–322 (2004). https://doi.org/10.1007/s00240-003-0360-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00240-003-0360-z

Keywords

Navigation