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Interleukin (IL)-11 Is Involved in the Functional Liaison between Breast Tumor Cells and the Surrounding Stroma †

Marianna Talia
Francesca Cirillo
Domenica Scordamaglia
Maria Francesca Santolla
Asia Spinelli
Salvatore De Rosis
Lucia Muglia
Azzurra Zicarelli
Anna Maria Miglietta
Marcello Maggiolini
1 and
Rosamaria Lappano
Department of Pharmacy, Health and Nutritional Sciences, University of Calabria, 87036 Rende, Italy
Breast Unit, Regional Hospital Cosenza, 87100 Cosenza, Italy
Author to whom correspondence should be addressed.
Presented at Cells, Cells and Nothing but Cells: Discoveries, Challenges and Directions, 6–8 March 2023; Available online:
Biol. Life Sci. Forum 2023, 21(1), 23;
Published: 27 March 2023


Current advances in molecular profiling methodologies and the accessibility of multi-omics datasets are paving the way toward a better understanding of heterogeneous diseases, including breast cancer (BC). In this regard, we sought to uncover the transcriptional changes triggered by estrogen and insulin in a primary BC cell line (BCAHC-1), which expresses the 46kDa isoform of the estrogen receptor (ER)α and the insulin receptor, as we have previously ascertained. Raw data from RNA sequencing of BCAHC-1 cells were processed by the Bcl2Fastq 2.20 version of the Illumina pipeline, while in silico analyses were performed in R Studio using the TCGA dataset. Real-time PCR, immunoblotting, ELISA and chromatin immunoprecipitation experiments were used to identify the molecular events triggered by estrogen and insulin in BCAHC-1 cells and cancer-associated fibroblasts (CAFs). Furthermore, migration and invasion assays allowed us to ascertain the mechanisms triggering these biological responses in the presence of the aforementioned hormone treatments. First, we determined that 17β-estradiol (E2) and insulin stimulate a peculiar IL-11 expression and IL-11 secretion in BCAHC-1 cells. Thereafter, bioinformatics analyses confirmed the up-regulation of IL-11 in ER-positive BCs, with respect to adjacent normal tissues, and its association with worse survival. Next, the involvement of IL-11 in pro-metastatic transduction signaling was established via pathway enrichment analyses. Notably, we found that the secretion of IL-11 by BCAHC-1 cells prompts an invasive phenotype of CAFs through the up-regulation of genes belonging to the extracellular matrix organization pathway, namely, the intercellular adhesion molecule 1 and integrin alpha 5. Overall, our findings indicate that IL-11 secretion by BC cells may elicit a paracrine action on the surrounding stroma and introduce invasive properties, suggesting that IL-11 could be considered a valuable target in comprehensive treatments of ER-positive BC patients.

Author Contributions

Conceptualization, M.T., F.C., M.M. and R.L.; methodology, M.T., F.C., D.S., M.M. and R.L.; software, M.T. and F.C.; validation, M.T., F.C. and R.L.; formal analysis, M.T.; investigation, M.T., F.C., D.S., M.F.S., A.S., S.D.R., L.M. and A.Z.; resources, A.M.M. and M.M.; data curation, M.T. and F.C.; writing—original draft preparation, M.T. and F.C.; writing—review and editing, M.M. and R.L.; visualization, M.M. and R.L.; supervision, M.M. and R.L.; funding acquisition, M.M. and R.L. All authors have read and agreed to the published version of the manuscript.


Fondazione AIRC supported M.M. (IG n. 21322) and R.L. (IG n. 27386). Ministero della Salute (Italy) supported M.M. and R.L. (project RF-2019-12368937).

Institutional Review Board Statement

The study was conducted in accordance with the Declaration of Helsinki and approved by the “Comitato Etico Ospedale Regionale, Cosenza, Italy” (approval code: 166, 2 December 2016).

Informed Consent Statement

Written informed consent has been obtained from the patients to publish this paper and the experimental research has been performed with the ethical approval provided by the “Comitato Etico Ospedale Regionale, Cosenza, Italy” (approval code: 166, 2 December 2016).

Data Availability Statement

Not applicable.


We would like to thank the special award, namely “Department of Excellence 2018-2022” (Italian Law 232/2016) at the Department of Pharmacy, Health and Nutritional Sciences of the University of Calabria (Italy) and the “Sistema Integrato di Laboratori per l’Ambiente–(SILA) PONa3_00341”.

Conflicts of Interest

The authors declare no conflict of interest.
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MDPI and ACS Style

Talia, M.; Cirillo, F.; Scordamaglia, D.; Santolla, M.F.; Spinelli, A.; De Rosis, S.; Muglia, L.; Zicarelli, A.; Miglietta, A.M.; Maggiolini, M.; et al. Interleukin (IL)-11 Is Involved in the Functional Liaison between Breast Tumor Cells and the Surrounding Stroma. Biol. Life Sci. Forum 2023, 21, 23.

AMA Style

Talia M, Cirillo F, Scordamaglia D, Santolla MF, Spinelli A, De Rosis S, Muglia L, Zicarelli A, Miglietta AM, Maggiolini M, et al. Interleukin (IL)-11 Is Involved in the Functional Liaison between Breast Tumor Cells and the Surrounding Stroma. Biology and Life Sciences Forum. 2023; 21(1):23.

Chicago/Turabian Style

Talia, Marianna, Francesca Cirillo, Domenica Scordamaglia, Maria Francesca Santolla, Asia Spinelli, Salvatore De Rosis, Lucia Muglia, Azzurra Zicarelli, Anna Maria Miglietta, Marcello Maggiolini, and et al. 2023. "Interleukin (IL)-11 Is Involved in the Functional Liaison between Breast Tumor Cells and the Surrounding Stroma" Biology and Life Sciences Forum 21, no. 1: 23.

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