Innovative In Vitro Model Sheds Light on How Tumor Cells Enter the Bloodstream

Recent research published in iScience has advanced our understanding of how cancer cells metastasize through the bloodstream. Led by researchers from the University of Tokyo, Kanazawa University, and Kyorin University School of Medicine, the study introduces a sophisticated three-dimensional in vitro system that mimics blood vessels and tumor tissue. This model enables scientists to observe the precise process by which clusters of tumor cells—detached from primary tumors—manage to infiltrate blood vessels and contribute to metastasis.

Metastasis remains one of the most challenging aspects of cancer treatment, often responsible for the poor prognosis associated with advanced cancers. Although circulating tumor cells (CTCs) are known to be involved—especially clusters of these cells that circulate within the blood—the mechanisms behind their entry into blood vessels were not fully understood.

Using live-imaging techniques, the team positioned tumor organoids either adjacent to or slightly away from artificial blood vessels and watched their interactions in real-time. The findings revealed that tumor cell clusters actively migrate toward blood vessel walls, disrupting their structure to facilitate entry. High levels of transforming growth factor-beta (TGF-β) and activin were expressed in vessel wall cells during this migration, prompting endothelial-to-mesenchymal transition—a process that weakens the vessel wall and enables tumor clusters to invade.

This partial dismantling of vascular structures not only allows tumor clusters to intravasate but also promotes their dispersal via the bloodstream, fueling metastasis. The insights gained from this model are pivotal because they point to the potential for developing treatments that prevent tumor cell clusters from breaching blood vessel barriers. Such strategies could significantly improve outcomes for patients with advanced cancer.

Overall, this innovative in vitro system offers a powerful platform for further studying how tumor cells invade blood vessels and for testing targeted therapies aimed at halting metastasis. Source: [https://medicalxpress.com/news/2025-05-vitro-cancer-reveals-tumor-cells.html]