Embedded Bioprinting of Breast Cancer-Adipose Composite Tissue Model for Patient-Specific Paracrine Interaction Analysis

Abstract

The interaction between breast cancer and stromal tissues varies significantly from patient to patient, greatly impacting cancer prognosis. However, conventional models struggle to accurately replicate these patient-specific interactions. Herein, a novel breast cancer-adipose composite tissue model capable of precisely adjusting the inter-tissue interaction is developed. The composite tissue model is produced through precise embedded bioprinting of breast-cancer spheroids and live-adipose-tissue ink. This model possessed not only precisely patterned cancer spheroids but also well-preserved intrinsic extracellular matrices (ECMs) and heterogeneous cell populations of adipose tissue (AT). Evaluation results successfully demonstrated that the bioprinted composite model can precisely regulate adipokine secretion, drug resistance, and cancer-cell invasion characteristics by adjusting the distance between the cancer spheroids and adipose tissue. The utility of the model is validated using adipokine-targeted therapies (C-compound/SC600125 (SC), AG 490 (AG), and Metformin (MET)). Interestingly, the inhibition of cancer cell proliferation and invasion by these adipokine-targeted drugs nearly doubled as the tissue distance decreased. This suggests that the efficacy of the drugs can be precisely evaluated using the new model. These findings underscore the potential of the developed composite model to replicate patient-specific crosstalk, thereby offering a promising platform for the sophisticated evaluation of various breast-cancer therapies.