Interleukin-6 Signaling in Triple Negative Breast Cancer Cells Elicits the Annexin A1/Formyl Peptide Receptor 1 Axis and Affects the Tumor Microenvironment
Lara Vecchi,
Sara Teixeira Soares Mota,
Mariana Alves Pereira Zóia,
Isabella Castro Martins,
Jessica Brito de Souza,
Tiago Góss Santos,
Adriano de Oliveira Beserra,
Victor Piana de Andrade,
Luiz Ricardo Goulart,
Thaise Gonçalves Araújo
Affiliations
Lara Vecchi
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Sara Teixeira Soares Mota
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Mariana Alves Pereira Zóia
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Isabella Castro Martins
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Jessica Brito de Souza
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Tiago Góss Santos
International Research Center, AC Camargo Cancer Center, 01509-900 São Paulo, Brazil
Adriano de Oliveira Beserra
International Research Center, AC Camargo Cancer Center, 01509-900 São Paulo, Brazil
Victor Piana de Andrade
Department of Investigative Pathology, AC Camargo Cancer Center, 01525-001 São Paulo, Brazil
Luiz Ricardo Goulart
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Thaise Gonçalves Araújo
Laboratory of Nanobiotechnology, Institute of Genetics and Biochemistry, Federal University of Uberlândia, Campus Umuarama, Bloco 2E, Sala 248, 38400-902 Uberlândia, Brazil
Annexin A1 (AnxA1) is a pleiotropic protein that exerts essential roles in breast cancer (BC) growth and aggressiveness. In our previous work, we described the autocrine signaling of AnxA1 through formyl peptide receptor 1 (FPR1) in the triple-negative (TN) BC cell line, MDA-MB-231. Here, we aimed to describe the interaction between the AnxA1/FPR1 and the Interleukin-6 (IL-6) signaling pathways and their role in the tumor microenvironment (TME). First, we demonstrated that AnxA1 and IL-6 expression levels are correlated in BC tissue samples. In three TNBC cell lines, overexpression of both AnxA1 and IL-6 was also identified. Next, we inhibited FPR1, the IL-6 receptor and STAT3 in both MDA-MB-231 and MDA-MB-157 cells. The FPR1 inhibition led to increased levels of IL-6 and secreted AnxA1 in both cell lines. On the other side, inhibition of the IL-6 receptor or STAT3 led to the impairment of AnxA1 secretion, suggesting the essential role of the IL-6 signaling cascade in the activation of the AnxA1/FPR1 autocrine axis. Finally, we described the interaction between IL-6 and the AnxA1/FPR1 pathways and their role on the TME by analyzing the effect of supernatants derived from MDA-MB-231 and MDA-MB-157 cells under the inhibition of FPR1 or IL-6 signaling on fibroblast cell motility.
