Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches
In this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3⁻9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA...
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| Format: | Article |
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MDPI AG
2019-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/11/2/242 |
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| author | Janette Beshay Peter Jantscheff Thomas Lemarchand Cynthia Obodozie Christoph Schächtele Holger Weber |
| author_facet | Janette Beshay Peter Jantscheff Thomas Lemarchand Cynthia Obodozie Christoph Schächtele Holger Weber |
| author_sort | Janette Beshay |
| collection | DOAJ |
| description | In this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3⁻9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA) or <i>N</i>-methyl-<i>N</i>-nitrosourea (MNU) as carcinogens. During necropsy, primary tumors and suspicious tissues were assessed macroscopically and re-transplanted (in PDX-like manner) into sex-matched syngeneic animals. Outgrowing tumors were histologically characterized as either spinocellular carcinoma (1/8) or various differentiated sarcomas (7/8). Growth curves of four sarcomas showed striking heterogeneity. These cMDIs were further characterized by flow cytometry, RNA sequencing, or efficacy studies. A variable invasion of immune cells into the tumors, as well as varying expression of tyrosine kinase receptor, IFN-γ signature, or immune cell population marker genes could be observed. Immune checkpoint inhibitor treatment (anti-mPD-1, anti-mCTLA-4, or a combination thereof) showed different responses in the various cMDI models. In general, cMDI models are carcinogen-induced tumors of low passage number that were propagated as tissue pieces in mice without any tissue culturing. Therefore, the tumors contained conserved tumor characteristics and intratumoral immune cell populations. In contrast to the previously described spontaneous MDI, carcinogen induction resulted in a greater number of individual but histologically related tumors, which were preferentially sarcomas. |
| first_indexed | 2024-03-12T19:18:09Z |
| format | Article |
| id | doaj.art-a23669c0cb9d47378710994ff6e491e0 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-12T19:18:09Z |
| publishDate | 2019-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-a23669c0cb9d47378710994ff6e491e02023-08-02T05:22:57ZengMDPI AGCancers2072-66942019-02-0111224210.3390/cancers11020242cancers11020242Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic ApproachesJanette Beshay0Peter Jantscheff1Thomas Lemarchand2Cynthia Obodozie3Christoph Schächtele4Holger Weber5In Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, GermanyIn Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, GermanyTPL Pathology Labs, Sasbacher Str. 10, 79111 Freiburg, GermanyIn Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, GermanyIn Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, GermanyIn Vivo Pharmacology, ProQinase GmbH, Breisacher Str. 117, 79106 Freiburg, GermanyIn this second study, we established syngeneic in vivo models named carcinogen-induced mouse-derived isografts (cMDIs). Carcinogen-induced tumors were obtained during short-term observation (3⁻9 months) of CBA/J mice treated with various administration routes with 3-methylcholanthrene (MCA) or <i>N</i>-methyl-<i>N</i>-nitrosourea (MNU) as carcinogens. During necropsy, primary tumors and suspicious tissues were assessed macroscopically and re-transplanted (in PDX-like manner) into sex-matched syngeneic animals. Outgrowing tumors were histologically characterized as either spinocellular carcinoma (1/8) or various differentiated sarcomas (7/8). Growth curves of four sarcomas showed striking heterogeneity. These cMDIs were further characterized by flow cytometry, RNA sequencing, or efficacy studies. A variable invasion of immune cells into the tumors, as well as varying expression of tyrosine kinase receptor, IFN-γ signature, or immune cell population marker genes could be observed. Immune checkpoint inhibitor treatment (anti-mPD-1, anti-mCTLA-4, or a combination thereof) showed different responses in the various cMDI models. In general, cMDI models are carcinogen-induced tumors of low passage number that were propagated as tissue pieces in mice without any tissue culturing. Therefore, the tumors contained conserved tumor characteristics and intratumoral immune cell populations. In contrast to the previously described spontaneous MDI, carcinogen induction resulted in a greater number of individual but histologically related tumors, which were preferentially sarcomas.https://www.mdpi.com/2072-6694/11/2/242mouse tumor modelsexperimental cancermouse-derived isografts (MDIs)carcinogen-induced tumorstherapyimmune checkpoint inhibitorsimmunocompetent animalssyngeneic |
| spellingShingle | Janette Beshay Peter Jantscheff Thomas Lemarchand Cynthia Obodozie Christoph Schächtele Holger Weber Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches Cancers mouse tumor models experimental cancer mouse-derived isografts (MDIs) carcinogen-induced tumors therapy immune checkpoint inhibitors immunocompetent animals syngeneic |
| title | Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches |
| title_full | Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches |
| title_fullStr | Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches |
| title_full_unstemmed | Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches |
| title_short | Mouse-Derived Isograft (MDI) In Vivo Tumor Models II. Carcinogen-Induced cMDI Models: Characterization and Cancer Therapeutic Approaches |
| title_sort | mouse derived isograft mdi in vivo tumor models ii carcinogen induced cmdi models characterization and cancer therapeutic approaches |
| topic | mouse tumor models experimental cancer mouse-derived isografts (MDIs) carcinogen-induced tumors therapy immune checkpoint inhibitors immunocompetent animals syngeneic |
| url | https://www.mdpi.com/2072-6694/11/2/242 |
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