Activation of IGF/IGF-IR signaling pathway fails to induce epithelial-mesenchymal transition in pancreatic cancer cells

• Published in: Pancreatology : official journal of the International Association of Pancreatology (IAP) ... [et al.] 2019-03, Vol.19 (2), p.390-396
• Main Authors: Kopantzev, E.P., Kopantseva, M.R., Grankina, E.V., Mikaelyan, A., Egorov, V.I., Sverdlov, E.D.
• Format: Article
• Language: English
• Subjects: AKT protein; Biomarkers, Tumor; Biotechnology; Cell Differentiation; Cell Line, Tumor; Cell proliferation; Chemotherapy; Drug resistance; Enzyme-linked immunosorbent assay; Epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - physiology; Experiments; Gene Expression Regulation, Neoplastic - drug effects; Genotype & phenotype; Humans; Immunoglobulins; Insulin-like growth factor I; Insulin-Like Growth Factor I - metabolism; Insulin-Like Growth Factor I - pharmacology; Kinases; Membranes; Mesenchyme; Metastases; Metastasis; Pancreatic cancer; Pancreatic ductal adenocarcinoma; Pancreatic Neoplasms - metabolism; Penicillin; Phenotypes; Phosphorylation; Proteins; Receptor, IGF Type 1 - metabolism; Signal transduction; Stromal cells; Transcription; Transforming Growth Factor beta2 - pharmacology; Tumor cell lines; Tumor microenvironment; Tumors
• ISSN: 1424-3903; 1424-3911
• DOI: 10.1016/j.pan.2019.01.010

Pancreatic cancer stromal cells produce various protein factors, which presumably provide cancer cells with drug resistance and may influence their ability to form metastasis via induction of epithelial-mesenchymal transition (ЕМТ). The goal of our project was to study the effects of IGF-I on expression of protein markers of epithelial and mesenchymal differentiation, and on expression of transcriptional regulators of EMT in pancreatic cancer cell lines. We used Western blot analysis to study the expression patterns of epithelial and mesenchymal protein markers in pancreatic cancer cell lines, which have been stimulated with IGF-I for various periods of time. The ELISA technique was employed to determine the concentration of IGF-I in conditioned media. Additionally, the effect of IGF-I on proliferation of pancreatic cancer cells was measured via MTS technique. We investigated the effect of IGF/IGF-IR signaling pathway activation on expression levels of cell differentiation markers in five pancreatic cancer cell lines (AsPC-1, BxPC-3, Capan-2, MiaPaCa-2 and Panc1). The IGF-I stimulation led to phosphorylation of IGF-IR and activation of PI-3K/Akt signaling cascade. At the same time our results reveal that the activation of IGF/IGF-IR signaling pathway in pancreatic cancer cells does not induce a significant shift in cell phenotype towards mesenchymal differentiation and does not induce a decrease in expression levels of epithelial protein markers. Our results demonstrate that IGF-I does not function as an effective inductor of EMT in pancreatic cancer cell lines and that stimulation of IGF-I/IGF-IR signaling pathway does not lead to EMT associated changes in cell differentiation.