Cell Spheroids with Enhanced Aggressiveness to Mimic Human Liver Cancer In Vitro and In Vivo
| Autor: | Hyun Mi Kang, Kyung-Sook Chung, Dong-Soo Im, Kyung Hee Noh, Ho-Joon Lee, Hong Ryul Jung, Nam-Soon Kim, Jung Hwa Lim, Jea Woon Ryu, Dae-Soo Kim, Hyun-Soo Cho, Cho Rok Jung, Eun Su Kim |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Carcinoma Hepatocellular Angiogenesis Cell Cell Culture Techniques lcsh:Medicine Biology Article 03 medical and health sciences Mice 0302 clinical medicine Cancer stem cell In vivo Cell Line Tumor Spheroids Cellular medicine Human Umbilical Vein Endothelial Cells Tumor Cells Cultured Tumor Microenvironment Animals Humans lcsh:Science neoplasms Tumor microenvironment Multidisciplinary Large cell Gene Expression Profiling Liver Neoplasms lcsh:R Spheroid Xenograft Model Antitumor Assays Coculture Techniques digestive system diseases Disease Models Animal 030104 developmental biology medicine.anatomical_structure Cell culture 030220 oncology & carcinogenesis embryonic structures Cancer research lcsh:Q Transcriptome |
| Zdroj: | Scientific Reports, Vol 7, Iss 1, Pp 1-14 (2017) Scientific Reports SCIENTIFIC REPORTS(7) |
| ISSN: | 2045-2322 |
| Popis: | We fabricated a spheroid-forming unit (SFU) for efficient and economic production of cell spheroids. We optimized the protocol for generating large and homogenous liver cancer cell spheroids using Huh7 hepatocellular carcinoma (HCC) cells. The large Huh7 spheroids showed apoptotic and proliferative signals in the centre and at the surface, respectively. In particular, hypoxia-induced factor-1 alpha (HIF-1α) and ERK signal activation were detected in the cell spheroids. To diminish core necrosis and increase the oncogenic character, we co-cultured spheroids with 2% human umbilical vein endothelial cells (HUVECs). HUVECs promoted proliferation and gene expression of HCC-related genes and cancer stem cell markers in the Huh7 spheroidsby activating cytokine signalling, mimicking gene expression in liver cancer. HUVECs induced angiogenesis and vessel maturation in Huh7 spheroids in vivo by activating epithelial–mesenchymal transition and angiogenic pathways. The large Huh7 cell spheroids containing HUVECs survived at higher concentrations of anti-cancer drugs (doxorubicin and sorafenib) than did monolayer cells. Our large cell spheroid provides a useful in vitro HCC model to enable intuitive observation for anti-cancer drug testing. |
| Databáze: | OpenAIRE |
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