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

Autor: Irina N. Druzhkova, Olga Rakitina, D. A. Didych, Eugene Sverdlov, Nadezhda I. Ignatova, I. V. Alekseenko, Maria M. Lukina, Varvara V. Dudenkova, Elena V. Zagaynova, George V. Sharonov, Sergey V. Kostrov, Dina R. Safina, A. I. Kuzmich, Marina V. Shirmanova
Rok vydání: 2020
Předmět:
Cell type
Epithelial-Mesenchymal Transition
Mice
Nude
Apoptosis
epithelial/mesenchymal state
Hybrid Cells
medicine.disease_cause
fibroblast activation
Article
Catalysis
lcsh:Chemistry
Inorganic Chemistry
Extracellular matrix
Mice
Biomarkers
Tumor
Tumor Cells
Cultured
medicine
Animals
Humans
Physical and Theoretical Chemistry
Fibroblast
lcsh:QH301-705.5
Molecular Biology
Spectroscopy
Cell Proliferation
colorectal cancer cells
Chemistry
Organic Chemistry
Mesenchymal stem cell
collagen remodeling
General Medicine
Fibroblasts
Xenograft Model Antitumor Assays
Coculture Techniques
Extracellular Matrix
Computer Science Applications
Cell biology
Gene Expression Regulation
Neoplastic
medicine.anatomical_structure
lcsh:Biology (General)
lcsh:QD1-999
Cell culture
Cancer cell
Cancer-Associated Fibroblasts
Female
Collagen
Colorectal Neoplasms
Carcinogenesis
cancer-associated fibroblasts
Zdroj: International Journal of Molecular Sciences
Volume 21
Issue 21
International Journal of Molecular Sciences, Vol 21, Iss 8119, p 8119 (2020)
ISSN: 1422-0067
DOI: 10.3390/ijms21218119
Popis: 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.
Databáze: OpenAIRE
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