Journal
SMALL
Volume 18, Issue 20, Pages -Publisher
WILEY-V C H VERLAG GMBH
DOI: 10.1002/smll.202107757
Keywords
3D cancer cell invasion; directional cancer cell migration; dynamic TGF-beta release; hydrogels; programmable multiple functions
Categories
Funding
- European Research Council (ERC) under the European Union [819424]
- Cancer Genomics Centre Netherlands (CGC.NL)
- European Research Council (ERC) [819424] Funding Source: European Research Council (ERC)
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In the research of cancer cell invasion and metastasis, the recreation of physiologically relevant and faithful three-dimensional tumor models remains a challenge. Here, a programmable multifunctional 3D cancer cell invasion microbuckets-hydrogel platform is developed, which successfully mimics the invasion process of cancer cells and demonstrates the relationship between single-cell migration and collective cell migration during the epithelial-mesenchymal transition. This platform has the potential to mimic the dynamically changing tumor microenvironment and has wide applications in cancer research, bio-fabrication, cell signaling, and drug screening.
In the research of cancer cell invasion and metastasis, recreation of physiologically relevant and faithful three-dimensional (3D) tumor models that recapitulate spatial architecture, spatiotemporal control of cell communication and signaling pathways, and integration of extracellular cues remains an open challenge. Here, a programmable multifunctional 3D cancer cell invasion microbuckets-hydrogel (Mb-H) platform is developed by integrating various function-variable microbuckets and extracellular matrix (ECM)-like hydrogels. Based on this Mb-H micro platform, the aggregation of multi-cancer cells is well controlled to form cancer cell spheroids, and the guiding relationship of single-cell migration and collective cell migration during the epithelial-mesenchymal transition (EMT) of cancer cell invasion are demonstrated. By programming and precisely assembling multiple functions in one system, the Mb-H platform with spatial-temporal controlled release of cytokine transforming growth factor beta (TGF-beta) and various functionalized Mb-H platforms with intelligent adjustment of cell-matrix interactions are engineered to coordinate the 3D invasive migration of cancer cell spheroids. This programmable and adaptable 3D cancer cell invasion micro platform takes a new step toward mimicking the dynamically changing (localized) tumor microenvironment and exhibits wide potential applications in cancer research, bio-fabrication, cell signaling, and drug screening.
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