期刊
SMALL METHODS
卷 5, 期 7, 页码 -出版社
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smtd.202100072
关键词
in situ 3D cell printing; metastatic cancer unit; precision cancer medicine; tissue-level platforms; vascular endothelium system
资金
- National Research Foundation of Korea [2019R1A3A3005437, 2020M3H4A1A02084827]
- National Research Foundation of Korea [2020M3H4A1A02084827, 2019R1A3A3005437] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
During tumor progression, the size and location of the tumor play a significant role in determining its metastatic potential. A novel tissue-level platform using in situ 3D cell printing was presented to study cancer-vascular interactions and investigate metastasis-associated changes. The platform enables precise positioning control and may open new possibilities for precision cancer medicine.
During tumor progression, the size and location of the tumor are important factors closely associated with the metastatic potential of the cancer as they largely govern tumor hypoxia and angiogenesis. However, despite the achievements of previous studies, these critical factors are poorly studied, mainly due to the lack of a flexible technique that can readily control 3D tumor mimicking constructs and their spatial relations with vasculature. Here, a novel tissue-level platform consisting of a metastatic cancer unit (MCU) and a perfusable vascular endothelium system (VES) is presented using in situ 3D cell printing. Size-tunable and position-controllable 3D cancer spheroids (500-1000 mu m) are directly printed within the established bath bioink with a self-driven perfusable vascular channel. The cancer-vascular interactions are generated through controlling the distance between MCU and VES to investigate metastasis-associated changes at adjacent and distal regions. The result shows that MCU in 600 mu m diameter includes hypoxia, invasion, and angiogenetic signaling. The further observations demonstrate that the proximity of MCU to VES augments the epithelial-mesenchymal transition (EMT) in MCU and vascular dysfunction/inflammation in VES, corroborating the positional significance in tumor metastasis. The platform with the precise-positioning control enables the recapitulation of patient's detailed metastatic progression, opening the chance for precision cancer medicine.
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