Skip to main content
Log in

TGFβ and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin

  • Papers
  • Published:
The Histochemical Journal Aims and scope Submit manuscript

Summary

Nodular palmar fibromatosis is a self-limited proliferation of fibro-/myofibroblasts associated with growth factor synthesis and abundant fibronectin extracellular matrix deposition. bFGF and TGFβ are potent modulators of fibro-/myofibroblast proliferation and differentiation. Moreover,in vitro investigations evidenced a TGFβ1-dependent regulation of alternative splicing of fibronectin mRNA. To investigate a possible implication of these growth factors in the tissue formation process of palmar fibromatosis, TGFβ1/2 and bFGF synthesis, as well as TGFβ1/3 and bFGF tissue distribution, is demonstrated by RNAin situ hybridization and/or immunohistochemistry in relation to myofibroblast phenotype development (α-smooth muscle actin, desmin immunohistochemistry), expression of different fibronectin isoforms (ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunohistochemistry, fibronectin RNAin situ hybridization) and cellular activity (cyclin RNAin situ hybridization, Ki-67 immunolabelling). The myofibroblast phenotype (α-smooth muscle actin, desmin), the growth factor synthesis (TGFβ1 and 2, bFGF), fibronectin matrix synthesis (RNAin situ hybridization with cDNA) and ED-A+, ED-B+ and oncofetal glycosylated fibronectin immunostaining are exclusively localized in the active proliferative nodules (Ki-67 immunolabelling and cyclin mRNA demonstration). Whereas the growth factor synthesis is restricted to the proliferative areas of the fibromatosis only, TGFβ1, TGFβ3 and bFGF proteins can also be detected immunohistochemically with a lower intensity in the surrounding aponeurotic tissue. The spatial correlation of myofibroblast phenotype, TGFβ and bFGF synthesis and the occurrence of the oncofetal molecular fibronectin variants (ED-B+ and oncofetal glycosylated fibronectin) in the active proliferative fibromatosis nodules suggests a pathogentic role of these growth factors and matrix components in the tumorous tissue formation process. The presence of the bFGF and TGFβ1/3 proteins in fibroblasts neighbouring the proliferative nodules may point to a recruitment of quiescent aponeurotic fibroblasts in the fibromatous tissue formation process.

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

Similar content being viewed by others

References

  • Adams,J. C. &Watt,F. M. (1993) Regulation of development and differentiation by the extracellular matrix.Development 117, 1183–98.

    CAS  PubMed  Google Scholar 

  • Bachem,M. G.,Sell,K. -M.,Melchior,R.,Kropf,J.,Eller,T. &Gressner,A. M. (1993) Tumor necrosis factor alpha (TNFα) and transforming growth factor β1 (TGFβ1) stimulate fibronectin synthesis and the transdifferentiation of fat-storing cells in the rat liver into myofibroblasts.Virchows Archiv. B Cell Pathol. 63, 123–30.

    CAS  Google Scholar 

  • Baird,A. &Walicke,P. (1989) Fibroblast growth factors.Br. Med. Bull. 45, 438–52.

    CAS  PubMed  Google Scholar 

  • Baird,K. S.,Crossan,J. F. &Ralston,S. H. (1993) Abnormal growth factor and cytokine expression in Dupuytren's contracture.J. Clin. Pathol. 46, 425–8.

    CAS  PubMed  Google Scholar 

  • Balza,E.,Borsi,L.,Allemanni,G. &Zardi,L. (1988) Transforming growth factor β regulates the level of different fibronectin isoforms in normal human cultured fibroblasts.FEBS Lett. 228, 42–4.

    Article  CAS  PubMed  Google Scholar 

  • Berndt,A.,Kosmehl,H. &Katenkapmp,D. (1993) Analyse der myofibroblastären Basallamina in der Proliferationsphase der Dupuytrenschen Palmarfibromatose.Verh. Dtsch. Ges. Path. 77, 389.

    Google Scholar 

  • Berndt,A.,Kosmehl,H.,Katenkamp,D. &Tauchmann,V. (1994) Appearance of the myofibroblastic phenotype in Dupuytren's disease is associated with a fibronectin, laminin, collagen type IV and tenascin extracellular matrix.Pathobiology 62, 55–8.

    CAS  PubMed  Google Scholar 

  • Bissell,M. J.,Hall,H. G. &Parry,G. (1982) How does the extracellular matrix direct gene expression?J. Theor. Biol. 99, 31–68.

    Article  CAS  PubMed  Google Scholar 

  • Björkerud,S. (1991) Effects of transforming growth factor-β1 on human arterial smooth muscle cellsin vitro.Arterioscler. Thromb. 11, 892–902.

    PubMed  Google Scholar 

  • Borsi,L.,Carnemolla,B.,Castellani,P.,Rossellini,C.,Vecchio,D.,Allemanni,G.,Chang,S. E.,Taylor-Papadimitriou,J.,Pande,H. &Zardi,L. (1987) Monoclonal antibodies in the analysis of fibronectin isoforms generated by alternative splicing of mRNA precursors in normal and transformed human cells cells.J. Cell. Biol. 104, 595–600.

    Article  CAS  PubMed  Google Scholar 

  • Borsi,L.,Castellani,P.,Risso,A. M.,Leprini,A. &Zardi,L. (1990) Transforming growth factor-β regulates the splicing pattern of fibronectin messenger RNA precursor.FEBS Lett. 261, 175–8.

    Article  CAS  PubMed  Google Scholar 

  • Burgess,W. H. &Maciag,T. (1989) The heparin-binding (fibroblast) growth factor family of proteins.Annu. Rev. Biochem. 58, 575–606.

    Article  CAS  PubMed  Google Scholar 

  • Carnemolla,B.,Balza,E.,Siri,A.,Zardi,L.,Nicotra,M. R.,Bigotti,A. &Natali,P. G. (1989) A tumor-associated fibronectin isoform generated by alternative splicing of messenger RNA precusors.J. Cell Biol. 108, 1139–48.

    Article  CAS  PubMed  Google Scholar 

  • Carnemolla,B.,Leprini,A.,Allemanni,G.,Saginati,M. &Zardi,L. (1992) The inclusion of the type III repeat ED-B in the fibronectin molecule generates conformational modifications that unmask a cryptic sequence.J. Biol Chem. 267, 24689–92.

    CAS  PubMed  Google Scholar 

  • David,L.,Mandel,U.,Clausen,H. &Sobrinhosimoes,M. (1993) Immunhistochemical expression of oncofetal fibronectin in benign and malignant lesions of the stomach.Eur. J. Cancer 29A, 2070–1.

    CAS  PubMed  Google Scholar 

  • Desmouliere,A.,Geinoz,A.,Gabbiani,F. &Gavviani,G. (1993) Transforming growth factor-β1 induces α-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts.J. Cell Biol. 122, 103–11.

    Article  CAS  PubMed  Google Scholar 

  • Eddy,R. J.,Petro,J. A. &Tomasek,J. J. (1988) Evidence for the nonmuscle nature of the ‘myofibroblast’ of granulation tissue and hypertropic scar. An immunofluorescence study.Am. J. Pathol. 130, 252–60.

    CAS  PubMed  Google Scholar 

  • Enenstein,J.,Waleh,N. S. &Kramer,R. H. (1992) Basic FGF and TGF-β differentially modulate integrin expression of human microvascular endothelial cells.Exp. Cell Res. 203, 499–503.

    Article  CAS  PubMed  Google Scholar 

  • Ffrench-Constant,C.,van deWater,L.,Dvorak,H. F. &Hynes,R. O. (1989) Reappearance of an embryonic pattern of fibronectin splicing during wound healing in the adult rat.J. Cell Biol. 109, 903–14.

    Article  CAS  PubMed  Google Scholar 

  • Gonzalez,A. -M.,Buscaglia,M.,Fox,R.,Isacchi,A.,Sarmientos,P.,Farris,J.,Ong,M.,Martineau,D.,Lappi,D. A. &Baird,A. (1992) Basic fibroblast growth factor in Dupuytren's contracture.Am. J. Pathol. 141, 661–71.

    CAS  PubMed  Google Scholar 

  • Grande,J.,Melder,D.,Zinsmeister,A. &Killen,P. (1993) Transforming growth factor-β1 induces collagen IV gene expression in NIH-3T3 cells.Lab. Invest. 69, 387–95.

    CAS  PubMed  Google Scholar 

  • Gustmann,C.,Altmannsberger,M.,Osborn,M.,Griesser,H. &Feller,A. C. (1991) Cytokeratin expression and vimentin content in large cell anaplastic lymphomas and other non-Hodgkin's lymphoma.Am. J. Pathol. 138, 1413–22.

    CAS  PubMed  Google Scholar 

  • Halliday,N. L.,Rayan,G. M.,Zardi,L. &TomasekJ. J. (1994) Distribution of ED-A and ED-B containing fibronectin isoforms in Dupuytren's disease.J. Hand. Surg. 19A, 428–34.

    Google Scholar 

  • Herlyn,M. &Malkowicz,S. B. (1991) Biology of disease. Regulatory pathways in tumor growth and invasion.Lab. Invest. 65 262–71.

    CAS  PubMed  Google Scholar 

  • Kornblihtt,A. R.,Vibe-Pedersen,K. &Baraville,F. E. (1983) Isolation and characterization of cDNA clones for human and bovine fibronectins.Proc. Natl Acad. Sci. USA 80, 3218–22.

    CAS  PubMed  Google Scholar 

  • Kornblihtt,A. R.,Umezawa,K.,Vibe-Pedersen,K. &Baralle,F. E. (1985) Primary structure of human fibronectin: Differential splicing may generate at least 10 polypeptides from a single gene.EMBO J. 4, 1755–9.

    CAS  PubMed  Google Scholar 

  • Kosmehl, H. Berndt, A., Katenkamp, D., Mandel, U., Bohle, R., Gabler, U. &Celeda, D. (1995) Differential expression of fibronectin splice variants, oncofetal glycosylated fibronectin and laminin isoforms in nodular palmar fibromatosis.Path. Res. Pract.,191, in press.

  • Luck,J. V. (1959) Dupuytren's contracture. A new concept of the pathogenesis correlated with surgical development.J. Bone Joint Surg. 41-A, 635–64.

    CAS  PubMed  Google Scholar 

  • Mandel,U.,Therkildsen,M. H.,Reibl,J.,Sweeney,B.,Matsuura,H.,Hakomori,S. -I.,Dabelsteen,E. &Clausen,H. (1992) Cancer-associated changes in glycosylation of fibronectin.APMIS 100, 817–26.

    CAS  PubMed  Google Scholar 

  • Okragly,A.,Balwit,J. M. &Haak-Frendscho,M. (1994) Transforming growth factor β 1 (TGFβ1): A biological paradox.Promega Notes 47, 10–14.

    Google Scholar 

  • Perosio,P. M. &Brooks,J. J. (1989) Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis.Lab. Invest. 60, 245–53.

    CAS  PubMed  Google Scholar 

  • Roholl,P. J. M.,Weima,S. M.,Prinsen,I.,DeWeger,R. A.,DenOtter,W. &VanUnnik,J. A. M. (1991) Expression of growth factors and their receptors on human sarcoma. Immunohistochemical detection of platelet-derived growth factor, epidermal growth factor and their receptors.Cancer J. 4, 83–8.

    Google Scholar 

  • Rønnov-Jessen,L. &Petersen,O. W. (1993) Induction of α-smooth muscle actin by transforming growth factor-β1 in quiescent human breast gland fibroblasts.Lab Invest. 68, 696–707.

    PubMed  Google Scholar 

  • Schürch,W.,SeemayerT. A. &GabbianiG. (1992) Myofibroblast. InHistology for Pathologists (edited bySterngerg,S. S.), pp. 109–44. New York: Raven Press.

    Google Scholar 

  • Schwarzbauer,J. E. (1991) Alternative splicing of fibronectin: three variants, three functions.BioEssays 13, 527–33.

    Article  CAS  PubMed  Google Scholar 

  • Singer,I. I. (1979) The fibronexus: A transmembrane association of fibronectin containing fibers and bundles of 5 nm microfilaments in hamster and human fibroblasts.Cell 16, 675–85.

    Article  CAS  PubMed  Google Scholar 

  • Sporn,M. B. &Roberts,A. B. (1988) Peptide growth factors are multifunctional.Nature 332, 217–19.

    Article  CAS  PubMed  Google Scholar 

  • Sporn,M. B.,Roberts,A. B.,Wakefield,L. M. &DeCrombrugghe,B. (1987) Some recent advances in the chemistry and biology of transforming growth factor-beta.J. Cell Biol. 105, 1039–331.

    Article  CAS  PubMed  Google Scholar 

  • Tan,E. M. L.,Hoffren,J.,Rouda,S.,Greenbaum,S.,Fox,J. W.Moore,J. H. &Dodge,G. R. (1993) Decorin, versican, and biglycan gene expression by keloid and normal dermal fibroblasts: differential regulation by basic fibroblast growth factor.Exp. Cell Res. 209, 200–7.

    Article  CAS  PubMed  Google Scholar 

  • Tomasek,J. J.,Schultz,R. J.,Episalla,C. W. &Newman,S. A. (1986) The cytoskeleton and extracellular matrix of the Dupuytren's disease ‘myofibroblast’: An immunofluorescence study of a nonmuscle cell type.J. Hand Surg. 11A, 365–71.

    Google Scholar 

  • Wang,A.,Cohen,D. S.,Palmer,E. &Sheppard,D. (1991) Polarized regulation of fibronectin secretion and alternative splicing by transforming growth factor β.J. Biol. Chem. 266, 15598–601.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Berndt, A., Kosmehl, H., Mandel, U. et al. TGFβ and bFGF synthesis and localization in Dupuytren's disease (nodular palmar fibromatosis) relative to cellular activity, myofibroblast phenotype and oncofetal variants of fibronectin. Histochem J 27, 1014–1020 (1995). https://doi.org/10.1007/BF02389692

Download citation

  • Received:

  • Revised:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02389692

Keywords

Navigation