RNA Sequencing Reveals Alterations and Similarities in Cell Metabolism, Hypoxia and Immune Evasion in Primary Cell Cultures of Clear Cell Renal Cell Carcinoma

Bibliographic Details
Title: RNA Sequencing Reveals Alterations and Similarities in Cell Metabolism, Hypoxia and Immune Evasion in Primary Cell Cultures of Clear Cell Renal Cell Carcinoma
Authors: Adrian Georg Simon, Laura Kristin Esser, Jörg Ellinger, Manuel Ritter, Glen Kristiansen, Michael H. Muders, Thomas Mayr, Marieta Ioana Toma
Source: Frontiers in Oncology, Vol 12 (2022)
Publisher Information: Frontiers Media S.A., 2022.
Publication Year: 2022
Collection: LCC:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
Subject Terms: in vitro model, cell culture conditions, ccRCC, RNA-Seq, renal cancer, patient-derived model, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
More Details: The treatment of advanced renal cell carcinoma remains a challenge. To develop novel therapeutic approaches, primary cell cultures as an in vitro model are considered more representative than commercial cell lines. In this study, we analyzed the gene expression of previously established primary cell cultures of clear cell renal cell carcinoma by bulk (3’m)RNA sequencing and compared it to the tissue of origin. The objectives were the identification of dysregulated pathways under cell culture conditions. Furthermore, we assessed the suitability of primary cell cultures for studying crucial biological pathways, including hypoxia, growth receptor signaling and immune evasion. RNA sequencing of primary cell cultures of renal cell carcinoma and a following Enrichr database analysis revealed multiple dysregulated pathways under cell culture conditions. 444 genes were significantly upregulated and 888 genes downregulated compared to the tissue of origin. The upregulated genes are crucial in DNA repair, cell cycle, hypoxia and metabolic shift towards aerobic glycolysis. A downregulation was observed for genes involved in pathways of immune cell differentiation and cell adhesion. We furthermore observed that 7275 genes have a similar mRNA expression in cell cultures and in tumor tissue, including genes involved in the immune checkpoint signaling or in pathways responsible for tyrosine kinase receptor resistance. Our findings confirm that primary cell cultures are a representative tool for specified experimental approaches. The results presented in this study give further valuable insights into the complex adaptation of patient-derived cells to a new microenvironment, hypoxia and other cell culture conditions, which are often neglected in daily research, and allow new translational and therapeutic approaches.
Document Type: article
File Description: electronic resource
Language: English
ISSN: 2234-943X
Relation: https://www.frontiersin.org/articles/10.3389/fonc.2022.883195/full; https://doaj.org/toc/2234-943X
DOI: 10.3389/fonc.2022.883195
Access URL: https://doaj.org/article/323f3dd02fd647e4b4cee5131361c30d
Accession Number: edsdoj.323f3dd02fd647e4b4cee5131361c30d
Database: Directory of Open Access Journals
More Details
ISSN:2234943X
DOI:10.3389/fonc.2022.883195
Published in:Frontiers in Oncology
Language:English