Signal transduction pathway analysis in desmoid-type fibromatosis

Transforming growth factor-β, COX2 and sex steroid receptors

Nicholas A. Mignemi, Doha M. Itani, John H. Fasig, Vicki L. Keedy, Kenneth R. Hande, Brent W. Whited, Kelly Cornett Homlar, Hernan Correa, Cheryl M. Coffin, Jennifer O. Black, Yajun Yi, Jennifer L. Halpern, Ginger E. Holt, Herbert S. Schwartz, Jonathan G. Schoenecker, Justin M.M. Cates

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Despite reports of sex steroid receptor and COX2 expression in desmoid-type fibromatosis, responses to single agent therapy with anti-estrogens and non-steroidal anti-inflammatory drugs are unpredictable. Perhaps combination pharmacotherapy might be more effective in desmoid tumors that co-express these targets. Clearly, further understanding of the signaling pathways deregulated in desmoid tumors is essential for the development of targeted molecular therapy. Transforming growth factor-β (TGFβ) and bone morphogenetic proteins (BMP) are important regulators of fibroblast proliferation and matrix deposition, but little is known about the TGFβ superfamily in fibromatosis. A tissue microarray representing 27 desmoid tumors was constructed; 14 samples of healing scar and six samples of normal fibrous tissue were included for comparison. Expression of selected receptors and activated downstream transcription factors of TGFβ family signaling pathways, β-catenin, sex steroid hormone receptors and COX2 were assessed using immunohistochemistry; patterns of co-expression were explored via correlational statistical analyses. In addition to β-catenin, immunoreactivity for phosphorylated SMAD2/3 (indicative of active TGFβ signaling) and COX2 was significantly increased in desmoid tumors compared with healing scar and quiescent fibrous tissue. Low levels of phosphorylated SMAD1/5/8 were detected in only a minority of cases. Transforming growth factor-β receptor type 1 and androgen receptor were expressed in both desmoid tumors and scar, but not in fibrous tissue. Estrogen receptor-β was present in all cases studied. Transforming growth factor-β signaling appears to be activated in desmoid-type fibromatosis and phosphorylated SMAD2/3 and COX2 immunoreactivity might be of diagnostic utility in these tumors. Given the frequency of androgen receptor, estrogen receptor-β and COX2 co-expression in desmoid tumors, further assessment of the efficacy of combination pharmacotherapy using hormonal agonists/antagonists together with COX2 inhibitors should be considered.

Original languageEnglish (US)
Pages (from-to)2173-2180
Number of pages8
JournalCancer Science
Volume103
Issue number12
DOIs
StatePublished - Dec 1 2012

Fingerprint

Aggressive Fibromatosis
Fibroma
Steroid Receptors
Transforming Growth Factors
Signal Transduction
Neoplasms
Cicatrix
Catenins
Androgen Receptors
Estrogen Receptors
Non-Steroidal Estrogens
Molecular Targeted Therapy
Drug Therapy
Bone Morphogenetic Proteins
Growth Factor Receptors
Cyclooxygenase 2 Inhibitors
Gonadal Steroid Hormones
Anti-Inflammatory Agents
Transcription Factors
Fibroblasts

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Mignemi, N. A., Itani, D. M., Fasig, J. H., Keedy, V. L., Hande, K. R., Whited, B. W., ... Cates, J. M. M. (2012). Signal transduction pathway analysis in desmoid-type fibromatosis: Transforming growth factor-β, COX2 and sex steroid receptors. Cancer Science, 103(12), 2173-2180. https://doi.org/10.1111/cas.12037

Signal transduction pathway analysis in desmoid-type fibromatosis : Transforming growth factor-β, COX2 and sex steroid receptors. / Mignemi, Nicholas A.; Itani, Doha M.; Fasig, John H.; Keedy, Vicki L.; Hande, Kenneth R.; Whited, Brent W.; Homlar, Kelly Cornett; Correa, Hernan; Coffin, Cheryl M.; Black, Jennifer O.; Yi, Yajun; Halpern, Jennifer L.; Holt, Ginger E.; Schwartz, Herbert S.; Schoenecker, Jonathan G.; Cates, Justin M.M.

In: Cancer Science, Vol. 103, No. 12, 01.12.2012, p. 2173-2180.

Research output: Contribution to journalArticle

Mignemi, NA, Itani, DM, Fasig, JH, Keedy, VL, Hande, KR, Whited, BW, Homlar, KC, Correa, H, Coffin, CM, Black, JO, Yi, Y, Halpern, JL, Holt, GE, Schwartz, HS, Schoenecker, JG & Cates, JMM 2012, 'Signal transduction pathway analysis in desmoid-type fibromatosis: Transforming growth factor-β, COX2 and sex steroid receptors', Cancer Science, vol. 103, no. 12, pp. 2173-2180. https://doi.org/10.1111/cas.12037
Mignemi, Nicholas A. ; Itani, Doha M. ; Fasig, John H. ; Keedy, Vicki L. ; Hande, Kenneth R. ; Whited, Brent W. ; Homlar, Kelly Cornett ; Correa, Hernan ; Coffin, Cheryl M. ; Black, Jennifer O. ; Yi, Yajun ; Halpern, Jennifer L. ; Holt, Ginger E. ; Schwartz, Herbert S. ; Schoenecker, Jonathan G. ; Cates, Justin M.M. / Signal transduction pathway analysis in desmoid-type fibromatosis : Transforming growth factor-β, COX2 and sex steroid receptors. In: Cancer Science. 2012 ; Vol. 103, No. 12. pp. 2173-2180.
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