3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition
Hypoxia in the tumor microenvironment (TME) is the leading cause of metastasis and chemoresistance in cancer cells. Numerous 3D in vitro models have been proposed to study hypoxic stress, but none have enabled sufficient analysis of hepatocellular carcinoma (HCC). Herein, a 3D in vitro tumor vascula...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
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Wiley-VCH
2021-12-01
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| Series: | Advanced NanoBiomed Research |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/anbr.202100078 |
| _version_ | 1797823763607191552 |
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| author | Jungeun Lim Hyeri Choi Jungho Ahn Noo Li Jeon |
| author_facet | Jungeun Lim Hyeri Choi Jungho Ahn Noo Li Jeon |
| author_sort | Jungeun Lim |
| collection | DOAJ |
| description | Hypoxia in the tumor microenvironment (TME) is the leading cause of metastasis and chemoresistance in cancer cells. Numerous 3D in vitro models have been proposed to study hypoxic stress, but none have enabled sufficient analysis of hepatocellular carcinoma (HCC). Herein, a 3D in vitro tumor vasculature model for HCC is introduced to investigate cellular responses and drug resistance under hypoxic conditions through high‐content screening. The hypoxic TME of vascularized HCC can be established by maintaining the platform in a hypoxia chamber and is used to analyze the diverse physiological responses of the TME to normoxia, hypoxia, and drug treatment. The proposed platform also demonstrates the hypoxic status naturally induced by 3D HCC spheroids for comparison with single HCC cells cultured in the hypoxia chamber. The results show that hypoxic stress in the HCC vasculature promotes angiogenesis, hypoxia‐inducible factor 1 (HIF‐1) expression, and proliferation; it also enhances drug resistance. The hypoxic tumor vasculature of the model generates cellular responses that are also expressed in the physiological hypoxic microenvironment of HCC. These findings suggest that our high‐content microfluidic platform can be applied as a powerful tool to develop anticancer therapeutics, which have remained elusive because of hypoxia in the TME. |
| first_indexed | 2024-03-13T10:28:45Z |
| format | Article |
| id | doaj.art-505b60401a884b669384e55632194b3b |
| institution | Directory Open Access Journal |
| issn | 2699-9307 |
| language | English |
| last_indexed | 2024-03-13T10:28:45Z |
| publishDate | 2021-12-01 |
| publisher | Wiley-VCH |
| record_format | Article |
| series | Advanced NanoBiomed Research |
| spelling | doaj.art-505b60401a884b669384e55632194b3b2023-05-19T03:06:29ZengWiley-VCHAdvanced NanoBiomed Research2699-93072021-12-01112n/an/a10.1002/anbr.2021000783D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic ConditionJungeun Lim0Hyeri Choi1Jungho Ahn2Noo Li Jeon3School of Mechanical and Aerospace Engineering Seoul National University Seoul 08826 South KoreaInterdisciplinary Program in Bioengineering Seoul National University Seoul 08826 South KoreaSchool of Mechanical and Aerospace Engineering Seoul National University Seoul 08826 South KoreaSchool of Mechanical and Aerospace Engineering Seoul National University Seoul 08826 South KoreaHypoxia in the tumor microenvironment (TME) is the leading cause of metastasis and chemoresistance in cancer cells. Numerous 3D in vitro models have been proposed to study hypoxic stress, but none have enabled sufficient analysis of hepatocellular carcinoma (HCC). Herein, a 3D in vitro tumor vasculature model for HCC is introduced to investigate cellular responses and drug resistance under hypoxic conditions through high‐content screening. The hypoxic TME of vascularized HCC can be established by maintaining the platform in a hypoxia chamber and is used to analyze the diverse physiological responses of the TME to normoxia, hypoxia, and drug treatment. The proposed platform also demonstrates the hypoxic status naturally induced by 3D HCC spheroids for comparison with single HCC cells cultured in the hypoxia chamber. The results show that hypoxic stress in the HCC vasculature promotes angiogenesis, hypoxia‐inducible factor 1 (HIF‐1) expression, and proliferation; it also enhances drug resistance. The hypoxic tumor vasculature of the model generates cellular responses that are also expressed in the physiological hypoxic microenvironment of HCC. These findings suggest that our high‐content microfluidic platform can be applied as a powerful tool to develop anticancer therapeutics, which have remained elusive because of hypoxia in the TME.https://doi.org/10.1002/anbr.202100078drug screeninghepatocellular carcinomashypoxiamicrofluidicsvascularized tumors |
| spellingShingle | Jungeun Lim Hyeri Choi Jungho Ahn Noo Li Jeon 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition Advanced NanoBiomed Research drug screening hepatocellular carcinomas hypoxia microfluidics vascularized tumors |
| title | 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition |
| title_full | 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition |
| title_fullStr | 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition |
| title_full_unstemmed | 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition |
| title_short | 3D High‐Content Culturing and Drug Screening Platform to Study Vascularized Hepatocellular Carcinoma in Hypoxic Condition |
| title_sort | 3d high content culturing and drug screening platform to study vascularized hepatocellular carcinoma in hypoxic condition |
| topic | drug screening hepatocellular carcinomas hypoxia microfluidics vascularized tumors |
| url | https://doi.org/10.1002/anbr.202100078 |
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