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Tissue mimetic 3D scaffold for breast tumor-derived organoid culture toward personalized chemotherapy

Nayak, Biswadeep and Balachander, Gowri Manohari and Manjunath, Sathish and Rangarajan, Annapoorni and Chatterjee, Kaushik (2019) Tissue mimetic 3D scaffold for breast tumor-derived organoid culture toward personalized chemotherapy. In: COLLOIDS AND SURFACES B-BIOINTERFACES, 180 . pp. 334-343.

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Official URL: https://dx.doi.org/10.1016/j.colsurfb.2019.04.056

Abstract

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.

Item Type: Journal Article
Additional Information: copyright for this article belongs to ELSEVIER SCIENCE BV
Keywords: Breast cancer; 3D culture; Personalized medicine; Organoids; Cancer associated fibroblasts
Department/Centre: Division of Biological Sciences > Molecular Reproduction, Development & Genetics
Division of Interdisciplinary Research > Centre for Biosystems Science and Engineering
Division of Mechanical Sciences > Materials Engineering (formerly Metallurgy)
Depositing User: Id for Latest eprints
Date Deposited: 20 Aug 2019 11:01
Last Modified: 20 Aug 2019 11:01
URI: http://eprints.iisc.ac.in/id/eprint/63294

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