Establishment of Translational Luciferase-Based Cancer Models to Evaluate Antitumoral Therapies

Luciferase (luc) bioluminescence (BL) is the most used light-emitting protein that has been engineered to be expressed in multiple cancer cell lines, allowing for the detection of tumor nodules in vivo as it can penetrate most tissues. The goal of this study was to develop an oncolytic adenovirus (O...

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Veröffentlicht in:International journal of molecular sciences 2024-09, Vol.25 (19), p.10418
Hauptverfasser: Ramos-Gonzalez, Martin R, Sirpu Natesh, Nagabhishek, Rachagani, Satyanarayana, Amos-Landgraf, James, Shirwan, Haval, Yolcu, Esma S, Gomez-Gutierrez, Jorge G
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container_issue 19
container_start_page 10418
container_title International journal of molecular sciences
container_volume 25
creator Ramos-Gonzalez, Martin R
Sirpu Natesh, Nagabhishek
Rachagani, Satyanarayana
Amos-Landgraf, James
Shirwan, Haval
Yolcu, Esma S
Gomez-Gutierrez, Jorge G
description Luciferase (luc) bioluminescence (BL) is the most used light-emitting protein that has been engineered to be expressed in multiple cancer cell lines, allowing for the detection of tumor nodules in vivo as it can penetrate most tissues. The goal of this study was to develop an oncolytic adenovirus (OAd)-resistant human triple-negative breast cancer (TNBC) that could express luciferase. Thus, when combining an OAd with chemotherapies or targeted therapies, we would be able to monitor the ability of these compounds to enhance OAd antitumor efficacy using BL in real time. The TNBC cell line HCC1937 was stably transfected with the plasmid pGL4.50[luc2/CMV/Hygro] (HCC1937/luc2). Once established, HCC1937/luc2 was orthotopically implanted in the 4th mammary gland fat pad of NSG (non-obese diabetic severe combined immunodeficiency disease gamma) female mice. Bioluminescence imaging (BLI) revealed that the HCC1937/luc2 cell line developed orthotopic breast tumor and lung metastasis over time. However, the integration of luc plasmid modified the HCC1937 phenotype, making HCC1937/luc2 more sensitive to OAdmCherry compared to the parental cell line and blunting the interferon (IFN) antiviral response. Testing two additional luc cell lines revealed that this was not a universal response; however, proper controls would need to be evaluated, as the integration of luciferase could affect the cells' response to different treatments.
doi_str_mv 10.3390/ijms251910418
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source MDPI - Multidisciplinary Digital Publishing Institute; MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central
subjects Adenoviridae - genetics
Adenoviruses
Animals
Bioluminescence
Breast cancer
Cancer research
Cancer therapies
Cell Line, Tumor
Cell lines
Drug utilization
Female
Genetic aspects
Genetic engineering
Genotype & phenotype
Humans
Infections
Interferon
Luciferase
Luciferases - genetics
Luciferases - metabolism
Luminescent Measurements - methods
Lung cancer
Measurement techniques
Medical research
Metastasis
Methods
Mice
Mice, Inbred NOD
Mice, SCID
Oncolytic Virotherapy - methods
Oncolytic Viruses - genetics
Physiology
Proteins
Translational research
Triple Negative Breast Neoplasms - drug therapy
Triple Negative Breast Neoplasms - genetics
Triple Negative Breast Neoplasms - pathology
Tumors
Xenograft Model Antitumor Assays
title Establishment of Translational Luciferase-Based Cancer Models to Evaluate Antitumoral Therapies
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