200P - A novel multi-organ on chip model for metastatic tumor biology understanding

Background

Understanding the complex biology of metastatic tumors is critical for advancing cancer biology research and improving therapeutic interventions. To address this challenge, we have developed a novel multi-organ-on-chip (Multi-OOC) platform designed to unravel the intricacies of breast to bone (B2B) metastatic tumor growth. This innovative platform integrates organ-specific tissue models fluidically interconnected to mimic the dynamic interactions between primary tumor and distant organ during metastasis. By replicating the physiological microenvironments of various target organs, our model provides a unique opportunity to investigate the entire metastatic cascade, from tumor cell dissemination, circulating tumor cells (CTCs) survival under flow and colonization. In order to support real-time monitoring of cellular infiltration and response to therapeutic agents in a multi-organ context optically transparent OOC device has been developed, compatible with the optical microscope observation.

Methods

A breast cancer cell laden hydrogel has been developed by using MDA-MB-231 cells with and without endothelial cells (HUVEC), forming the capillary network. A computational fluid dynamic simulation was done to set up the proper capillary velocity and induced shear stresses. In a second chamber, a bone tissue model was developed as metastasis target: different ratio of hydroxyapatite (HA) has been included in a polymeric matrix to introduce a bone like mineral phase. Tumor cell infiltration and CTC survival rate have been monitored using different fluid-dynamic conditions and HA content.

Results

A multicompartmental OOC has been developed and successfully validated. The 3D breast cancer model displayed long term (2 months) survival in vitro in dynamic conditions, and a cells cytoskeleton reorganization was highlighted. The CTCs survival was shown correlated to the shear stresses induced by the fluid flow into the Multi-OOC. Different levels of CTCs infiltration in the mineralized matrix hosted in the metastatic OOC chamber were observed.

Conclusions

This platform holds great promise for accelerating the development of targeted therapies and personalized treatment strategies, ultimately advancing our understanding of metastatic cancer biology.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

M. Aiello, S. Scaglione: Financial Interests, Personal, Member of Board of Directors: React4life. All other authors have declared no conflicts of interest.