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Tytuł pozycji:

Expression of EMT-Related Genes in Hybrid E/M Colorectal Cancer Cells Determines Fibroblast Activation and Collagen Remodeling.

Tytuł:
Expression of EMT-Related Genes in Hybrid E/M Colorectal Cancer Cells Determines Fibroblast Activation and Collagen Remodeling.
Autorzy:
Druzhkova I; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.
Shirmanova M; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.
Ignatova N; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.
Dudenkova V; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.
Lukina M; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.
Zagaynova E; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.; Lobachevsky State University of Nizhny Novgorod, 603950 Nizhny Novgorod, Russia.
Safina D; Department of Molecular-Genetic Basis of Biotechnology and Protein Engineering, Institute of Molecular Genetics of National Research Centre «Kurchatov Institute», 123182 Moscow, Russia.
Kostrov S; Department of Molecular-Genetic Basis of Biotechnology and Protein Engineering, Institute of Molecular Genetics of National Research Centre «Kurchatov Institute», 123182 Moscow, Russia.
Didych D; Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of The Russian Academy of Sciences, 117997 Moscow, Russia.
Kuzmich A; Department of Molecular-Genetic Basis of Biotechnology and Protein Engineering, Institute of Molecular Genetics of National Research Centre «Kurchatov Institute», 123182 Moscow, Russia.; Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of The Russian Academy of Sciences, 117997 Moscow, Russia.
Sharonov G; Research Institute of Experimental Oncology and Biomedical Technologies, Privolzhsky Research Medical University, 603005 Nizhny Novgorod, Russia.; Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of The Russian Academy of Sciences, 117997 Moscow, Russia.; Institute of Translational Medicine, Pirogov Russian National Research Medical University, 117997 Moscow, Russia.
Rakitina O; Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of The Russian Academy of Sciences, 117997 Moscow, Russia.
Alekseenko I; Department of Molecular-Genetic Basis of Biotechnology and Protein Engineering, Institute of Molecular Genetics of National Research Centre «Kurchatov Institute», 123182 Moscow, Russia.; Department of Genomics and Postgenomic Technologies, Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry of The Russian Academy of Sciences, 117997 Moscow, Russia.; Laboratory of Epigenetics, FSBI «National Medical Research Center for Obstetrics, Gynecology and Perinatology named after Academician V.I. Kulakov» Ministry of Healthcare of the Russian Federation, 117198 Moscow, Russia.
Sverdlov E; Department of Molecular-Genetic Basis of Biotechnology and Protein Engineering, Institute of Molecular Genetics of National Research Centre «Kurchatov Institute», 123182 Moscow, Russia.; National Research Center «Kurchatov Institute», 123182 Moscow, Russia.
Źródło:
International journal of molecular sciences [Int J Mol Sci] 2020 Oct 30; Vol. 21 (21). Date of Electronic Publication: 2020 Oct 30.
Typ publikacji:
Journal Article
Język:
English
Imprint Name(s):
Original Publication: Basel, Switzerland : MDPI, [2000-
MeSH Terms:
Epithelial-Mesenchymal Transition*
Biomarkers, Tumor/*metabolism
Cancer-Associated Fibroblasts/*pathology
Collagen/*metabolism
Colorectal Neoplasms/*pathology
Fibroblasts/*pathology
Hybrid Cells/*pathology
Animals ; Apoptosis ; Biomarkers, Tumor/genetics ; Cancer-Associated Fibroblasts/metabolism ; Cell Proliferation ; Coculture Techniques ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/metabolism ; Extracellular Matrix ; Female ; Fibroblasts/metabolism ; Gene Expression Regulation, Neoplastic ; Humans ; Hybrid Cells/metabolism ; Mice ; Mice, Nude ; Tumor Cells, Cultured ; Xenograft Model Antitumor Assays
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Grant Information:
17-00-00194 (17-00-00190) Russian Foundation for Basic Research; 17-00-00194 (17-00-00189) Russian Foundation for Basic Research; 17-00-00194 (17-00-00193) Russian Foundation for Basic Research
Contributed Indexing:
Keywords: cancer-associated fibroblasts; collagen remodeling; colorectal cancer cells; epithelial/mesenchymal state; fibroblast activation
Substance Nomenclature:
0 (Biomarkers, Tumor)
9007-34-5 (Collagen)
Entry Date(s):
Date Created: 20201104 Date Completed: 20210326 Latest Revision: 20210326
Update Code:
20240105
PubMed Central ID:
PMC7662237
DOI:
10.3390/ijms21218119
PMID:
33143259
Czasopismo naukowe
Collagen, the main non-cellular component of the extracellular matrix (ECM), is profoundly reorganized during tumorigenesis and has a strong impact on tumor behavior. The main source of collagen in tumors is cancer-associated fibroblasts. Cancer cells can also participate in the synthesis of ECM; however, the contribution of both types of cells to collagen rearrangements during the tumor progression is far from being clear. Here, we investigated the processes of collagen biosynthesis and remodeling in parallel with the transcriptome changes during cancer cells and fibroblasts interactions. Combining immunofluorescence, RNA sequencing, and second harmonic generation microscopy, we have explored the relationships between the ratio of epithelial (E) and mesenchymal (M) components of hybrid E/M cancer cells, their ability to activate fibroblasts, and the contributions of both cell types to collagen remodeling. To this end, we studied (i) co-cultures of colorectal cancer cells and normal fibroblasts in a collagen matrix, (ii) patient-derived cancer-associated fibroblasts, and (iii) mouse xenograft models. We found that the activation of normal fibroblasts that form dense collagen networks consisting of large, highly oriented fibers depends on the difference in E/M ratio in the cancer cells. The more-epithelial cells activate the fibroblasts more strongly, which correlates with a dense and highly ordered collagen structure in tumors in vivo. The more-mesenchymal cells activate the fibroblasts to a lesser degree; on the other hand, this cell line has a higher innate collagen remodeling capacity. Normal fibroblasts activated by cancer cells contribute to the organization of the extracellular matrix in a way that is favorable for migratory potency. At the same time, in co-culture with epithelial cancer cells, the contribution of fibroblasts to the reorganization of ECM is more pronounced. Therefore, one can expect that targeting the ability of epithelial cancer cells to activate normal fibroblasts may provide a new anticancer therapeutic strategy.
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