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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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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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.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms251910418</identifier><identifier>PMID: 39408747</identifier><language>eng</language><publisher>Switzerland: MDPI AG</publisher><subject>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</subject><ispartof>International journal of molecular sciences, 2024-09, Vol.25 (19), p.10418</ispartof><rights>COPYRIGHT 2024 MDPI AG</rights><rights>2024 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2024 by the authors. 2024</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><cites>FETCH-LOGICAL-c330t-49f8c674dba5b14d57e5d6391e6ac94f99f11684c759e754350236f5b6facafa3</cites><orcidid>0000-0003-2535-7746 ; 0000-0002-1657-9470 ; 0000-0003-3610-260X ; 0000-0002-4794-0417 ; 0000-0002-4312-8798</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476533/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC11476533/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/39408747$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ramos-Gonzalez, Martin R</creatorcontrib><creatorcontrib>Sirpu Natesh, Nagabhishek</creatorcontrib><creatorcontrib>Rachagani, Satyanarayana</creatorcontrib><creatorcontrib>Amos-Landgraf, James</creatorcontrib><creatorcontrib>Shirwan, Haval</creatorcontrib><creatorcontrib>Yolcu, Esma S</creatorcontrib><creatorcontrib>Gomez-Gutierrez, Jorge G</creatorcontrib><title>Establishment of Translational Luciferase-Based Cancer Models to Evaluate Antitumoral Therapies</title><title>International journal of molecular sciences</title><addtitle>Int J Mol Sci</addtitle><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.</description><subject>Adenoviridae - genetics</subject><subject>Adenoviruses</subject><subject>Animals</subject><subject>Bioluminescence</subject><subject>Breast cancer</subject><subject>Cancer research</subject><subject>Cancer therapies</subject><subject>Cell Line, Tumor</subject><subject>Cell lines</subject><subject>Drug utilization</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic engineering</subject><subject>Genotype & phenotype</subject><subject>Humans</subject><subject>Infections</subject><subject>Interferon</subject><subject>Luciferase</subject><subject>Luciferases - genetics</subject><subject>Luciferases - metabolism</subject><subject>Luminescent Measurements - methods</subject><subject>Lung cancer</subject><subject>Measurement techniques</subject><subject>Medical research</subject><subject>Metastasis</subject><subject>Methods</subject><subject>Mice</subject><subject>Mice, Inbred NOD</subject><subject>Mice, SCID</subject><subject>Oncolytic Virotherapy - methods</subject><subject>Oncolytic Viruses - genetics</subject><subject>Physiology</subject><subject>Proteins</subject><subject>Translational research</subject><subject>Triple Negative Breast Neoplasms - drug therapy</subject><subject>Triple Negative Breast Neoplasms - genetics</subject><subject>Triple Negative Breast Neoplasms - pathology</subject><subject>Tumors</subject><subject>Xenograft Model Antitumor Assays</subject><issn>1422-0067</issn><issn>1661-6596</issn><issn>1422-0067</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2024</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>BENPR</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNpdkc2PFCEQxYnRuB969Go68eKlFZqv5mRmJ7NqMsbLeCbVNOwwoZsR6E3872Xcdd31AiT1q1f1eAi9IfgDpQp_9Icpd5woghnpn6FzwrquxVjI54_eZ-gi5wPGHe24eonOqGK4l0yeI73JBYbg836yc2mia3YJ5hyg-DhDaLaL8c4myLa9qsfYrGE2NjXf4mhDbkpsNrcQFii2Wc3Fl2WKqbbt9rXn6G1-hV44CNm-vr8v0Y_rzW79pd1-__x1vdq2hlJcWqZcb4Rk4wB8IGzk0vJRUEWsAKOYU8oRInpmJFdWckZ59SIcH4QDAw7oJfp0p3tchsmOppqpe-hj8hOkXzqC108rs9_rm3irCWFScEqrwvt7hRR_LjYXPflsbAgw27hkTQmRuI6WvKLv_kMPcUn1u_5QQkjc4f4fdQPBaj-7WAebk6he9aSTUlB60mrvKJNizsm6h50J1qeE9ZOEK__2sdEH-m-k9Dd5u6Hu</recordid><startdate>20240927</startdate><enddate>20240927</enddate><creator>Ramos-Gonzalez, Martin R</creator><creator>Sirpu Natesh, Nagabhishek</creator><creator>Rachagani, Satyanarayana</creator><creator>Amos-Landgraf, James</creator><creator>Shirwan, Haval</creator><creator>Yolcu, Esma S</creator><creator>Gomez-Gutierrez, Jorge G</creator><general>MDPI AG</general><general>MDPI</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>8G5</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>GUQSH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2O</scope><scope>MBDVC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-2535-7746</orcidid><orcidid>https://orcid.org/0000-0002-1657-9470</orcidid><orcidid>https://orcid.org/0000-0003-3610-260X</orcidid><orcidid>https://orcid.org/0000-0002-4794-0417</orcidid><orcidid>https://orcid.org/0000-0002-4312-8798</orcidid></search><sort><creationdate>20240927</creationdate><title>Establishment of Translational Luciferase-Based Cancer Models to Evaluate Antitumoral Therapies</title><author>Ramos-Gonzalez, Martin R ; Sirpu Natesh, Nagabhishek ; Rachagani, Satyanarayana ; Amos-Landgraf, James ; Shirwan, Haval ; Yolcu, Esma S ; Gomez-Gutierrez, Jorge G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c330t-49f8c674dba5b14d57e5d6391e6ac94f99f11684c759e754350236f5b6facafa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2024</creationdate><topic>Adenoviridae - 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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.</abstract><cop>Switzerland</cop><pub>MDPI AG</pub><pmid>39408747</pmid><doi>10.3390/ijms251910418</doi><orcidid>https://orcid.org/0000-0003-2535-7746</orcidid><orcidid>https://orcid.org/0000-0002-1657-9470</orcidid><orcidid>https://orcid.org/0000-0003-3610-260X</orcidid><orcidid>https://orcid.org/0000-0002-4794-0417</orcidid><orcidid>https://orcid.org/0000-0002-4312-8798</orcidid><oa>free_for_read</oa></addata></record> |
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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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