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The following is a summary of “Proteomic profiling and functional analysis of extracellular vesicles from metastasis-competent circulating tumor cells in colon cancer,” published in the March 2025 issue of the Journal of Experimental & Clinical Cancer Research by Cortés-Hernández et al.

Circulating tumor cells (CTCs) play a crucial role in cancer progression and metastasis, making them valuable models for investigating the biological mechanisms underlying disease evolution. This study aimed to characterize extracellular vesicles (EVs) derived from CTC lines established from a patient with metastatic colorectal cancer (mCRC) at different stages of disease progression, particularly after therapy failure. By analyzing EVs from these CTCs, researchers sought to understand their role in tumor dissemination and potential clinical implications. Morphological and size analyses revealed distinct variations among EVs from different CTC lines, suggesting a dynamic adaptation of tumor cells as they evolve under therapeutic pressure. Comparative proteomic profiling, referenced against the Vesiclepedia database, demonstrated an enrichment of proteins associated with cancer stemness, endosomal biogenesis, and poor mCRC prognosis. 

Notably, integrin family proteins were highly enriched in EVs from CTCs obtained after therapy resistance developed, indicating a potential link between treatment failure and enhanced metastatic capabilities. Further in vivo investigations assessed the biodistribution of these EVs, demonstrating their preferential accumulation in the liver, followed by the lungs, kidneys, and bones, particularly the femurs, highlighting organotropism patterns in metastatic spread. These findings suggest that EVs derived from CTCs may serve as functional mediators of metastasis, influencing organ-specific colonization of tumor cells. This study represents a pioneering effort in elucidating therapy-associated changes in CTC-derived EVs using an in vitro model, offering novel insights into their role as key drivers of cancer dissemination. 

While these results provide valuable mechanistic perspectives, further validation in patients with mCRC is necessary to fully establish the clinical relevance of CTC-derived EVs in metastasis. Understanding the molecular signatures and functional properties of these vesicles may ultimately contribute to the development of targeted therapeutic strategies aimed at mitigating cancer progression.

Source: jeccr.biomedcentral.com/articles/10.1186/s13046-025-03360-4