Exosomes are microvesicles that contain and transport coding and non-coding RNA, DNA, and proteins. They are secreted by several cell types, including tumor cells, and captured by receptor cells in a target organ, where they modify the tissue microenvironment, forming a pre-metastatic niche where circulating tumor cells can anchor. It has recently been found that blood from a tumor-draining vein can provide more reliable information about biomarkers than that obtained from a peripheral vein (PV). Venous return from the colon occurs through the mesenteric veins (MV), making the MV an excellent source to analyze potential biomarkers contained in exosomes released by the tumor cells in colon cancer before they reach the target organ. We have assessed the presence of exosomal proteins in the MV and PV of surgically resected colon cancer patients and correlated our findings with time to relapse (TTR).
On the day of surgery, blood samples were obtained from the MV and PV of 31 stage I-III colon cancer patients. Exosomes were isolated by ultracentrifugation and confirmed by cryogenic transmission electron microscopy. High-throughput proteomic analysis by mass spectrometry was used to identify expression levels of exosomal proteins. Findings were confirmed by western blot in MV and PV samples, as well as in samples from healthy controls, using TSG101 as a recognized marker of exosomes.
TSG101 was more highly expressed in relapsed patients than in non-relapsed patients or controls. The ECM1 protein was more highly expressed in both MV and PV exosomes from patients than in those from controls. However, ECM1 expression was 13 times higher in relapsed than in non-relapsed patients in MV – but not PV – exosomes. Among 17 patients with low exosomal ECM1 levels in MV, TTR was 40.2 months, compared to 31.3 months for 14 patients with high levels (P = 0.04).
ECM1 and TSG101 are higher expressed in relapsed patients and high expression of exosomal ECM1 released by the tumor is associated with shorter TTR. The analysis of exosomes isolated from the tumor-draining vein, the MV, is a promising method for the identification of biomarkers before reaching the target organ.
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University of Barcelona
University of Barcelona
All authors have declared no conflicts of interest.