Effects of transforming growth factor-B1 and tumour necrosis factor-A on cultured fibroblasts from skin fibroma as modulated by toremifene

Cinzia Lilli, Lorella Marinucci, Silvia Bellocchio, Domenico Ribatti, Chiara Balducci, Tiziano Baroni, Lucio Cagini, Giammario Giustozzi, Paola Locci

Research output: Contribution to journalArticle

Abstract

To determine how toremifene, an anti-oestrogen triphenylethylene derivate, reduces tumour mass, we investigated its modulation of TGF-β1 and TNF-α in fibroma fibroblasts. Normal and fibroma fibroblasts, isolated from patients affected by Gardner's syndrome without or with fibroma manifestation, were cultured in vitro. Secretion of GAG, collagen and TGF-β1 was increased in fibroma fibroblasts compared to healthy cells. The increase in TGF-β1 secretion into the medium was associated with a parallel increase in TGF-β1 gene expression and receptor number. Receptor cross-linking studies using radiolabelled TGF-β1 revealed more receptors, particularly types I and II, in fibroma fibroblasts than in normal cells. Normal and fibroma fibroblasts did not synthesise TNF-α, but they had TNF-α membrane receptors, as shown by TNF-α assay. TNF-α secreted by human monocytes, which may be present in the peritumoral area, increased cell proliferation and GAG accumulation and was, in turn, enhanced by TGF-β1 treatment. Both growth factors increased angiogenesis, as shown by the CAM assay. Toremifene reduced TGF-β1 secretion by fibroma fibroblasts and TNF-α secretion by monocytes, thus downregulating cell proliferation, ECM macromolecule accumulation and angiogenic progression. We hypothesise that increased TGF-β1 gene expression and TGF-β1 secretion in fibroma fibroblasts as well as the subsequent rise in TNF-α production by monocytes may facilitate fibroma growth and that toremifene inhibits autocrine and paracrine growth factor production.

Original languageEnglish
Pages (from-to)824-832
Number of pages9
JournalInternational Journal of Cancer
Volume98
Issue number6
DOIs
Publication statusPublished - Apr 20 2002

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Keywords

  • Fibroblasts
  • Fibroma
  • TGF-β1
  • TNF-β
  • Toremifene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Lilli, C., Marinucci, L., Bellocchio, S., Ribatti, D., Balducci, C., Baroni, T., Cagini, L., Giustozzi, G., & Locci, P. (2002). Effects of transforming growth factor-B1 and tumour necrosis factor-A on cultured fibroblasts from skin fibroma as modulated by toremifene. International Journal of Cancer, 98(6), 824-832. https://doi.org/10.1002/ijc.10306