Mimicking Tumor Metastasis Using a Transwell-Integrated Organoids-On-a-Chip Platform.

ABSTRACT

The mortality rate among cancer patients is primarily attributed to tumor metastasis. The evaluation of metastasis potential provides a powerful framework for personalized therapies. However, little work has so far been undertaken to precisely model tumor metastasis in vitro, hindering the development of preventive and therapeutic interventions. In this work, a tumor-metastasis-mimicked Transwell-integrated organoids-on-a-chip platform (TOP) for precisely evaluating tumor metastatic potential is developed. Unlike the conventional Transwell device for detecting cell migration, the engineered device facilitates the assessment of metastasis in patient-derived organoids (PDO). Furthermore, a novel Transwell chamber with a hexagon-shaped structure is developed to mimic the migration of tumor cells into surrounding tissues, allowing for the evaluation of tumor metastasis in a horizontal direction. As a proof-of-concept demonstration, tumor organoids and metastatic clusters are further evaluated at the protein, genetic, and phenotypic levels. In addition, preliminary drug screening is undertaken to highlight the potential for using the device to combat cancers. In summary, the tumor-metastasis-mimicked TOP offers unique capabilities for evaluating the metastasis potential of tumor organoids and contributes to the development of personalized cancer therapies.