Fabrication of a Coculture Organoid Model in the Biomimetic Matrix of Alginate to Investigate Breast Cancer Progression in a TAMs-Leading Immune Microenvironment

The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell–cell or cell–ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comp...

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Bibliographic Details
Published in:ACS applied materials & interfaces 2024-03, Vol.16 (9), p.11275-11288
Main Authors: Xu, Nian-Yuan, Li, Jun, Wang, Mei-Ling, Chen, Xue-Yu, Tang, Ruizhi, Liu, Xi-Qiu
Format: Article
Language:English
Subjects:
Biological and Medical Applications of Materials and Interfaces
Biomimetics
Breast Neoplasms - pathology
Cell Line, Tumor
Coculture Techniques
Cryogels - metabolism
Female
Humans
Macrophages - metabolism
Phosphatidylinositol 3-Kinases - metabolism
Tumor Microenvironment
Tumor-Associated Macrophages - metabolism
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Summary:The current research models of breast cancer are usually limited in their capacity to recapitulate the tumor microenvironment in vitro. The lack of an extracellular matrix (ECM) oversimplifies cell–cell or cell–ECM cross-talks. Moreover, the lack of tumor-associated macrophages (TAMs), that can comprise up to 50% of some solid neoplasms, poses a major problem for recognizing various hallmarks of cancer. To address these concerns, a type of direct breast cancer cells (BCCs)–TAMs coculture organoid model was well developed by a sequential culture method in this study. Alginate cryogels were fabricated with appropriate physical and mechanical properties to serve as an alternative ECM. Then, our previous experience was leveraged to polarize TAMs inside of the cryogels for creating an in vitro immune microenvironment. The direct coculture significantly enhanced BCCs organoid growth and cancer aggressive phenotypes, including the stemness, migration, ECM remodeling, and cytokine secretion. Furthermore, transcriptomic analysis and protein–protein interaction networks implied certain pathways (PI3K-Akt pathway, MAPK signaling pathway, etc.) and targets (TNF, PPARG, TLR2, etc.) during breast cancer progression in a TAM-leading immune microenvironment. Future studies to advance treatment strategies for BCC patients may benefit from using this facile model to reveal and target the interactions between cancer signaling and the immune microenvironment.
ISSN:1944-8244
1944-8252
DOI:10.1021/acsami.3c17863