E P Kopantzev1, M R Kopantseva2, E V Grankina2, A Mikaelyan3, V I Egorov4, E D Sverdlov5. 1. M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia; A. V. Vishnevsky Institute of Surgery, Ul. B. Serpuchovskaya 27, 115998, Moscow, Russia. Electronic address: kopantzev@ibch.ru. 2. M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia; A. V. Vishnevsky Institute of Surgery, Ul. B. Serpuchovskaya 27, 115998, Moscow, Russia. 3. Institute of Developmental Biology, Russian Academy of Sciences, Ul. Vavilova 26, 119991, Moscow, Russia; Skolkovo Institute of Science and Technology, Skolkovo Innovation Center, Skolkovo, 143025, Russia. 4. M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia; Bakhrushin Brothers Moscow City Hospital, Department of Surgical Oncology, Ul. Stromynka 7, 107014, Moscow, Russia. 5. M. M. Shemyakin and Yu. A. Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Ul. Miklukho-Maklaya 16/10, 117997, Moscow, Russia.
Abstract
BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND: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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Armel H Nwabo Kamdje; Paul F Seke Etet; Richard Simo Tagne; Lorella Vecchio; Kiven Erique Lukong; Mauro Krampera Journal: Front Cell Dev Biol Date: 2020-11-19
Authors: Armel H Nwabo Kamdje; Paul F Seke Etet; Richard Tagne Simo; Lorella Vecchio; Kiven Erique Lukong; Mauro Krampera Journal: Cancer Biol Med Date: 2020-12-15 Impact factor: 4.248