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3D Bioprinted Models for Predicting Chemotherapy Response in Colorectal Cancer With/Without Liver Metastases

ABSTRACT: The therapeutic regimens of adjuvant and neoadjuvant chemotherapy for colorectal cancer (CRC) remain largely relied on clinical experience, and thus preclinical models are needed to guide individualized medicine. The investigators are going to establish 3D bioprinted CRC models and organoids from surgically resected tumor tissues of CRC patients with or without liver metastases. In vitro 3D models and organoids will be treated with the same chemotherapy drugs with the corresponding patients from whom the models are derived. The sensitivity of chemotherapy drugs will be tested in these two types of in vitro models, and the actual response to chemotherapy in patients will be evaluated. The predictive ability of 3D models for chemotherapy sensitivity in CRC patients will be compared with that of the organoids. This observational study will validate the potential value of 3D bioprinted tumor models in predicting the response to chemotherapy in CRC.

DISEASE(S): Neoplasm Metastasis,Colorectal Cancer,Colorectal Neoplasms,Colorectal Cancer Liver Metastasis,Liver Neoplasms

PROVIDER: 2367475 | ecrin-mdr-crc |

REPOSITORIES: ECRIN MDR

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Project description:The traditional method for studying cancer in vitro is to grow immortalized cancer cells in two-dimensional (2D) monolayers on plastic. However, many cellular features are impaired in these unnatural conditions and big alterations in gene expression in comparison to tumors have been reported. Three-dimensional (3D) cell culture models have become increasingly popular and are suggested to be better models than 2D monolayers due to improved cell-to-cell contacts and structures that resemble in vivo architecture. The aim of this study was to develop a simple high-throughput 3D drug screening method and to compare drug responses in JIMT1 breast cancer cells when grown in 2D, in polyHEMA coated anchorage independent 3D models and in Matrigel on-top 3D cell culture models. We screened 102 compounds with multiple concentrations and biological replicates for their effects on cell proliferation. The cells were either treated immediately upon plating or they were allowed to grow in 3D for four days prior to the drug treatment. Big variations in drug responses were observed between the models indicating that comparisons of culture model influenced drug sensitivities cannot be made based on effects of a single drug. However, we show with the 63 most prominent drugs that, in general, JIMT1 cells grown on Matrigel were significantly more sensitive to drugs than cells grown in 2D cultures, while responses of cells grown in polyHEMA resembled those of 2D. Furthermore, comparison of gene expression profiles of the cell culture models to xenograft tumors indicated that cells cultured in Matrigel and as xenografts most closely resembled each other. In this study we also suggest that 3D cultures can provide a platform for systematic experimentation of larger compound collections in a high-throughput mode and be used as alternatives for traditional 2D screens towards better comparability to in vivo state. Gene expression analysis of JIMT1 breast cancer cells cultured as xenografts for 43 days, in two dimensional cultures for seven days (2D7d), in polyHEMA three dimensional cell culture models for four and seven days (PH7d and PH7d), and in Matrigel three dimensional cultures for four and seven days (MG4d and MG7d). Two biological replicates was included for each sample.

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3D Bioprinted Models for Predicting Chemotherapy Response in Colorectal Cancer With/Without Liver Metastases

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