Abstract 4577: An innovative platform to mimic the tumoral vascular microenvironment (TME) of patients with metastatic colorectal cancer (mCRC) using bioprinted hydrogel microfluidics

Abstract

Abstract Introduction: Metastasis involves a set of complex events that finally result in malignant cells from primary tumors invading distant tissues by the pass of circulant tumor cells (CTC) through the blood circulation. To authentically comprehend the complex chain of events and even enable new therapeutic approaches in mCRC patients, ex-vivo functional models are an unmet research need. Experimental Plan: PROMISE project is combining bioengineering solutions such as bioprinting biomaterials and microfluidics to mimic the tumor microenvironment (TME) of metastatic sites in mCRC. In this project, we are developing a bioprinted hydrogel-based microfluidic device that recapitulates this TME. Then, CTCs are isolated from mCRC patients, cultured, and characterized by microdroplet technology. Those CTCs are then infused on the biodegradable polymer that mimics vascular channels and surrounding stromal cells, through microfluidic connection, in order to mimic CTC-endothelial interactions, study the procedures of extravasation (the invasiveness potential of extravasated patient-derived CTCs into TME) and intravasation (the process of CTCs-derived and biopsy-derived tumor spheroids from the TME to the vascular channel). The photopolymerizable hydrogel mimics vascular structures, supporting the growth of HUVEC cells, and is printed in a cost-effective manner (30 minutes) using a semi-direct printing method with visible light. The CROSS chip is used for fast and efficient isolation of CTCs from unprocessed blood of mCRC patients. In parallel, multi-omics of mCRC are done in circulant tumor DNA (ctDNA) and tumor biopsy of mCRC, therefore correlating the phenotypic and genetic profile of the patient cohorts studied. A first pilot test has been carried out successfully obtaining blood from mCRc refractory patients, and excellent coordination between the multidisciplinary consortium has been achieved to draw blood from the patient, isolate CTCs and infuse them into the hydrogel. Extravasation and intravasation studies are ongoing. Conclusion: This multidisciplinary project, which brings together bioengineering, microfluidic, and oncology experts’ teams, is developing a successful ex-vivo, in vitro, and dynamic model that will permit a better study and understanding of the metastatic process in mCRC, from the process of intravasation to extravasation of CTCs, passing thought the better multi-omic characterization of CTCs and ctDNA. Citation Format: Nadia Saoudi González, Francesc Salvà Ballabrera, Ariadna García, Javier Gonzalo-Ruiz, Iosune Baraibar, Javier Ros, Marta Rodriguez, María García Díaz, Marta Falcó Fusté, Melika Parchehbaf Kashani, Carlos Honrado, Alar Ainla, Josep Tabernero, Lorena Diéguez, Elena Martínez Fraiz, Elena Élez. An innovative platform to mimic the tumoral vascular microenvironment (TME) of patients with metastatic colorectal cancer (mCRC) using bioprinted hydrogel microfluidics. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4577.