Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer

Luigi Strizzi, Katharine M. Hardy, Naira V. Margaryan, David W. Hillman, Elisabeth A. Seftor, Beiyun Chen, Xochiquetzal J. Geiger, E Aubrey Thompson, Wilma L. Lingle, Cathy A. Andorfer, Edith A. Perez, Mary J C Hendrix

Research output: Contribution to journalArticle

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Abstract

Introduction: The re-emergence of the tumour growth factor-beta (TGF-beta)-related embryonic morphogen Nodal has recently been reported in several different human cancers. In this study, we examined the expression of Nodal in a series of benign and malignant human breast tissues to determine the clinical significance of this expression and whether Nodal could represent a potential therapeutic target in breast cancer.Methods: Tissue sections from 431 therapeutically naive patients diagnosed with benign or malignant breast disease were stained for Nodal by immunohistochemistry and analysed in a blinded manner. The degree of Nodal staining was subsequently correlated with available clinical data, such as diagnoses and disease stage. These tissue findings were further explored in breast cancer cell lines MDA-MB-231 and MDA-MB-468 treated with a Nodal blocking antibody to determine biological effects for target validation.Results: A variable degree of Nodal staining was detected in all samples. The intensity of Nodal staining was significantly greater in undifferentiated, advanced stage, invasive breast cancer compared with benign breast disease or early stage breast cancer. Treatment of human breast cancer cells in vitro with Nodal blocking antibody significantly reduced proliferation and colony-forming ability in soft agar, concomitant with increased apoptosis.Conclusions: These data suggest a potential role for Nodal as a biomarker for disease progression and a promising target for anti-Nodal therapy in breast cancer.

Original languageEnglish (US)
Article numberR75
JournalBreast Cancer Research
Volume14
Issue number3
DOIs
StatePublished - May 11 2012

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Biomarkers
Breast Neoplasms
Breast Diseases
Blocking Antibodies
Staining and Labeling
Agar
Disease Progression
Neoplasms
Intercellular Signaling Peptides and Proteins
Breast
Therapeutics
Immunohistochemistry
Apoptosis
Cell Line

ASJC Scopus subject areas

  • Cancer Research
  • Oncology
  • Medicine(all)

Cite this

Strizzi, L., Hardy, K. M., Margaryan, N. V., Hillman, D. W., Seftor, E. A., Chen, B., ... Hendrix, M. J. C. (2012). Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer. Breast Cancer Research, 14(3), [R75]. https://doi.org/10.1186/bcr3185

Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer. / Strizzi, Luigi; Hardy, Katharine M.; Margaryan, Naira V.; Hillman, David W.; Seftor, Elisabeth A.; Chen, Beiyun; Geiger, Xochiquetzal J.; Thompson, E Aubrey; Lingle, Wilma L.; Andorfer, Cathy A.; Perez, Edith A.; Hendrix, Mary J C.

In: Breast Cancer Research, Vol. 14, No. 3, R75, 11.05.2012.

Research output: Contribution to journalArticle

Strizzi, L, Hardy, KM, Margaryan, NV, Hillman, DW, Seftor, EA, Chen, B, Geiger, XJ, Thompson, EA, Lingle, WL, Andorfer, CA, Perez, EA & Hendrix, MJC 2012, 'Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer', Breast Cancer Research, vol. 14, no. 3, R75. https://doi.org/10.1186/bcr3185
Strizzi, Luigi ; Hardy, Katharine M. ; Margaryan, Naira V. ; Hillman, David W. ; Seftor, Elisabeth A. ; Chen, Beiyun ; Geiger, Xochiquetzal J. ; Thompson, E Aubrey ; Lingle, Wilma L. ; Andorfer, Cathy A. ; Perez, Edith A. ; Hendrix, Mary J C. / Potential for the embryonic morphogen Nodal as a prognostic and predictive biomarker in breast cancer. In: Breast Cancer Research. 2012 ; Vol. 14, No. 3.
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