Journal
COLLOIDS AND SURFACES B-BIOINTERFACES
Volume 180, Issue -, Pages 334-343Publisher
ELSEVIER
DOI: 10.1016/j.colsurfb.2019.04.056
Keywords
Breast cancer; 3D culture; Personalized medicine; Organoids; Cancer associated fibroblasts
Funding
- Council for Scientific and Industrial Research (CSIR), India
- DBT-IISc partnership programme
- Wellcome Trust/DBT India Alliance Fellowship
- DST-FIST
- UGC, Govt. of India
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Breast cancer cell lines lose the inherent gene expression profiles of their source tumor and when cultured as monolayers (two-dimensional) are unable to represent patient tumors. Thus, we engineered a biochemico- and mechano-mimetic three-dimensional (3D) culture platform for primary breast cancer cells by decellularizing cancer-associated fibroblasts (CAFs) cultured on 3D macroporous polymer scaffolds to recapitulate tumor behavior and drug response more realistically. The presence of the CAF-derived extracellular matrix deposited on the polycaprolactone scaffold promoted cell attachment and viability, which is ascribed to higher levels of phosphorylated Focal Adhesion Kinase that mediates cell attachment via integrins. Single cells from primary breast cancers self-organized into tumoroids on prolonged culture. Response of the tumoroids to two chemotherapeutic drugs, doxorubicin and mitoxanthrone, varied significantly across patient samples. This model could be used as an ex vivo platform to culture primary cells toward developing effective and personalized chemotherapy regimens.
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