Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models
3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2020-12-01
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| Series: | Frontiers in Bioengineering and Biotechnology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2020.579896/full |
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| author | Leonie Gronbach Philipp Jurmeister Philipp Jurmeister Monika Schäfer-Korting Ulrich Keilholz Ingeborg Tinhofer Ingeborg Tinhofer Christian Zoschke |
| author_facet | Leonie Gronbach Philipp Jurmeister Philipp Jurmeister Monika Schäfer-Korting Ulrich Keilholz Ingeborg Tinhofer Ingeborg Tinhofer Christian Zoschke |
| author_sort | Leonie Gronbach |
| collection | DOAJ |
| description | 3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main disadvantages of the matrices commonly used for in vitro culture are their limited cultivation time and the low comparability with patient-specific matrix properties. Extended cultivation periods are feasible when primary human cells produce the extracellular matrix in situ. Herein, we adapted the hyalograft-3D approach from reconstructed human skin to normal and tumor oral mucosa models and compared the results to bovine collagen-based models. The hyalograft models showed similar morphology and cell proliferation after 7 weeks compared to collagen-based models after 2 weeks of cultivation. Tumor thickness and VEGF expression increased in hyalograft-based tumor models, whereas expression of laminin-332, tenascin C, and hypoxia-inducible factor 1α was lower than in collagen-based models. Taken together, the in situ produced extracellular matrix better confined tumor invasion in the first part of the cultivation period, with continuous tumor proliferation and increasing invasion later on. This proof-of-concept study showed the successful transfer of the hyalograft approach to tumor oral mucosa models and lays the foundation for the assessment of long-term drug treatment effects. Moreover, the use of an animal-derived extracellular matrix is avoided. |
| first_indexed | 2024-12-16T13:11:44Z |
| format | Article |
| id | doaj.art-a536ccfff6f943158c8516679c0220a9 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-12-16T13:11:44Z |
| publishDate | 2020-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-a536ccfff6f943158c8516679c0220a92022-12-21T22:30:36ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852020-12-01810.3389/fbioe.2020.579896579896Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa ModelsLeonie Gronbach0Philipp Jurmeister1Philipp Jurmeister2Monika Schäfer-Korting3Ulrich Keilholz4Ingeborg Tinhofer5Ingeborg Tinhofer6Christian Zoschke7Institute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, GermanyInstitute of Pathology, Berlin Institute of Health, Humboldt-Universität zu Berlin, Corporate Member of Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyHeidelberg and German Cancer Consortum Partner Site Berlin, German Cancer Research Center, Berlin, GermanyInstitute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, GermanyComprehensive Cancer Center, Berlin Institute of Health, Humboldt-Universität zu Berlin, Corporate Member of Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyHeidelberg and German Cancer Consortum Partner Site Berlin, German Cancer Research Center, Berlin, GermanyDepartment of Radiooncology and Radiotherapy, Berlin Institute of Health, Humboldt-Universität zu Berlin, Corporate Member of Freie Universität Berlin, Charité – Universitätsmedizin Berlin, Berlin, GermanyInstitute of Pharmacy (Pharmacology and Toxicology), Freie Universität Berlin, Berlin, Germany3D tumor models clearly outperform 2D cell cultures in recapitulating tissue architecture and drug response. However, their potential in understanding treatment efficacy and resistance development should be better exploited if also long-term effects of treatment could be assessed in vitro. The main disadvantages of the matrices commonly used for in vitro culture are their limited cultivation time and the low comparability with patient-specific matrix properties. Extended cultivation periods are feasible when primary human cells produce the extracellular matrix in situ. Herein, we adapted the hyalograft-3D approach from reconstructed human skin to normal and tumor oral mucosa models and compared the results to bovine collagen-based models. The hyalograft models showed similar morphology and cell proliferation after 7 weeks compared to collagen-based models after 2 weeks of cultivation. Tumor thickness and VEGF expression increased in hyalograft-based tumor models, whereas expression of laminin-332, tenascin C, and hypoxia-inducible factor 1α was lower than in collagen-based models. Taken together, the in situ produced extracellular matrix better confined tumor invasion in the first part of the cultivation period, with continuous tumor proliferation and increasing invasion later on. This proof-of-concept study showed the successful transfer of the hyalograft approach to tumor oral mucosa models and lays the foundation for the assessment of long-term drug treatment effects. Moreover, the use of an animal-derived extracellular matrix is avoided.https://www.frontiersin.org/articles/10.3389/fbioe.2020.579896/fullextracellular matrixhead and neck canceroral mucosapersonalized medicinetissue engineeringtumor microenvironment |
| spellingShingle | Leonie Gronbach Philipp Jurmeister Philipp Jurmeister Monika Schäfer-Korting Ulrich Keilholz Ingeborg Tinhofer Ingeborg Tinhofer Christian Zoschke Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models Frontiers in Bioengineering and Biotechnology extracellular matrix head and neck cancer oral mucosa personalized medicine tissue engineering tumor microenvironment |
| title | Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models |
| title_full | Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models |
| title_fullStr | Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models |
| title_full_unstemmed | Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models |
| title_short | Primary Extracellular Matrix Enables Long-Term Cultivation of Human Tumor Oral Mucosa Models |
| title_sort | primary extracellular matrix enables long term cultivation of human tumor oral mucosa models |
| topic | extracellular matrix head and neck cancer oral mucosa personalized medicine tissue engineering tumor microenvironment |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2020.579896/full |
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