Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer

Vivian Labovsky, Leandro Marcelo Martinez, María de Luján Calcagno, Kevin Mauro Davies, Hernán García-Rivello, Alejandra Wernicke, Leonardo Feldman, María Belén Giorello, Ayelén Matas, Francisco Raúl Borzone, Scott Howard, Norma Alejandra Chasseing

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Abstract

Spindle-shaped stromal cells, like carcinoma-associated fibroblasts and mesenchymal stem cells, influence tumor behavior and can serve as parameters in the clinical diagnosis, therapy, and prognosis of early breast cancer. Therefore, the aim of this study is to explore the clinicopathological significance of tumor necrosis factor-related apoptosis-induced ligand (TRAIL) receptors (Rs) 2 and 4 (TRAIL-R2 and R4), and interleukin-6 R (IL-6R) in spindle-shaped stromal cells, not associated with the vasculature, as prognostic determinants of early breast cancer patients. Receptors are able to trigger the migratory activity, among other functions, of these stromal cells. We conducted immunohistochemical analysis for the expression of these receptors in spindle-shaped stromal cells, not associated with the vasculature, of primary tumors from early invasive breast cancer patients, and analyzed their association with clinicopathological characteristics. Here, we demonstrate that the elevated levels of TRAIL-R2, TRAIL-R4, and IL-6R in these stromal cells were significantly associated with a higher risk of metastatic occurrence (p = 0.034, 0.026, and 0.006; respectively). Moreover, high expression of TRAIL-R4 was associated with shorter disease-free survival and metastasis-free survival (p = 0.013 and 0.019; respectively). Also, high expression of IL-6R was associated with shorter disease-free survival, metastasis-free survival, and overall survival (p = 0.003, 0.001, and 0.003; respectively). Multivariate analysis showed that IL-6R expression was an independent prognostic factor for disease-free survival and metastasis-free survival (p = 0.035). This study is the first to demonstrate that high levels of IL-6R expression in spindle-shaped stromal cells, not associated with the vasculature, could be used to identify early breast cancer patients with poor outcomes.

Original languageEnglish (US)
Pages (from-to)13377-13384
Number of pages8
JournalTumor Biology
Volume37
Issue number10
DOIs
StatePublished - Oct 1 2016

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Interleukin-6 Receptors
Stromal Cells
Interleukin-6
Breast Neoplasms
TNF-Related Apoptosis-Inducing Ligand Receptors
Disease-Free Survival
Survival
Neoplasm Metastasis
Mesenchymal Stromal Cells
Neoplasms
Multivariate Analysis
Tumor Necrosis Factor-alpha
Fibroblasts
Apoptosis
Ligands
Carcinoma

All Science Journal Classification (ASJC) codes

  • Cancer Research

Cite this

Labovsky, V., Martinez, L. M., Calcagno, M. D. L., Davies, K. M., García-Rivello, H., Wernicke, A., ... Chasseing, N. A. (2016). Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer. Tumor Biology, 37(10), 13377-13384. https://doi.org/10.1007/s13277-016-5268-7

Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer. / Labovsky, Vivian; Martinez, Leandro Marcelo; Calcagno, María de Luján; Davies, Kevin Mauro; García-Rivello, Hernán; Wernicke, Alejandra; Feldman, Leonardo; Giorello, María Belén; Matas, Ayelén; Borzone, Francisco Raúl; Howard, Scott; Chasseing, Norma Alejandra.

In: Tumor Biology, Vol. 37, No. 10, 01.10.2016, p. 13377-13384.

Research output: Contribution to journalArticle

Labovsky, V, Martinez, LM, Calcagno, MDL, Davies, KM, García-Rivello, H, Wernicke, A, Feldman, L, Giorello, MB, Matas, A, Borzone, FR, Howard, S & Chasseing, NA 2016, 'Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer', Tumor Biology, vol. 37, no. 10, pp. 13377-13384. https://doi.org/10.1007/s13277-016-5268-7
Labovsky V, Martinez LM, Calcagno MDL, Davies KM, García-Rivello H, Wernicke A et al. Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer. Tumor Biology. 2016 Oct 1;37(10):13377-13384. https://doi.org/10.1007/s13277-016-5268-7
Labovsky, Vivian ; Martinez, Leandro Marcelo ; Calcagno, María de Luján ; Davies, Kevin Mauro ; García-Rivello, Hernán ; Wernicke, Alejandra ; Feldman, Leonardo ; Giorello, María Belén ; Matas, Ayelén ; Borzone, Francisco Raúl ; Howard, Scott ; Chasseing, Norma Alejandra. / Interleukin-6 receptor in spindle-shaped stromal cells, a prognostic determinant of early breast cancer. In: Tumor Biology. 2016 ; Vol. 37, No. 10. pp. 13377-13384.
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