Possibility for Transcriptional Targeting of Cancer-Associated Fibroblasts-Limitations and Opportunities

Overview

Journal Int J Mol Sci

Publisher MDPI

Specialties Biochemistry
Chemistry
Molecular Biology

Date 2021 Apr 3

PMID 33804861

Citations 4

Authors

Dina V Antonova

Marina V Zinovyeva

Liya G Kondratyeva

Alexander V Sass

Irina V Alekseenko

Victor V Pleshkan

Affiliations

Soon will be listed here.

Abstract

Cancer-associated fibroblasts (CAF) are attractive therapeutic targets in the tumor microenvironment. The possibility of using CAFs as a source of therapeutic molecules is a challenging approach in gene therapy. This requires transcriptional targeting of transgene expression by cis-regulatory elements (CRE). Little is known about which CREs can provide selective transgene expression in CAFs. We hypothesized that the promoters of , , , , , , and genes, the expression of whose is increased in CAFs, could be used for transcriptional targeting. Analysis of the transcription of the corresponding genes revealed that unique transcription in model CAFs was characteristic for the and genes. However, none of the promoters in luciferase reporter constructs show selective activity in these fibroblasts. The CTGF, IGFBP2, JAG1, and SPARC promoters can provide higher transgene expression in fibroblasts than in cancer cells, but the nonspecific viral promoters CMV, SV40, and the recently studied universal PCNA promoter have the same features. The patterns of changes in activity of various promoters relative to each other observed for human cell lines were similar to the patterns of activity for the same promoters both in vivo and in vitro in mouse models. Our results reveal restrictions and features for CAF transcriptional targeting.

Citing Articles

Define cancer-associated fibroblasts (CAFs) in the tumor microenvironment: new opportunities in cancer immunotherapy and advances in clinical trials.

Zhang H, Yue X, Chen Z, Liu C, Wu W, Zhang N Mol Cancer. 2023; 22(1):159.

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Spheroids of FAP-Positive Cell Lines as a Model for Screening Drugs That Affect FAP Expression.

Pleshkan V, Zinovyeva M, Antonova D, Alekseenko I Biomedicines. 2023; 11(7).

PMID: 37509656 PMC: 10377737. DOI: 10.3390/biomedicines11072017.

Efficiency of Promoters of Human Genes and at Organism Level in a Model.

Selina P, Alekseenko I, Kurtova A, Pleshkan V, Voronezhskaya E, Demidyuk I Int J Mol Sci. 2023; 24(8).

PMID: 37108352 PMC: 10138699. DOI: 10.3390/ijms24087192.

Cell-specific expression of the gene is regulated by enhancer elements.

Antonova D, Gnatenko D, Kotova E, Pleshkan V, Kuzmich A, Didych D Front Mol Biosci. 2023; 10:1111511.

PMID: 36825204 PMC: 9941708. DOI: 10.3389/fmolb.2023.1111511.

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