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Detection and Monitoring of Tumor Associated Circulating DNA in Patient Biofluids
Published on: June 8, 2019
Circulating tumour-derived microvesicles in plasma of gastric cancer patients
Jaroslaw Baran1, Monika Baj-Krzyworzeka, Kazimierz Weglarczyk
1Department of Clinical Immunology, Polish-American Institute of Paediatrics, Jagiellonian University Medical College, Wielicka Str. 265, 30-663, Cracow, Poland.
Abstract:
Cell membrane microfragments called microvesicles (MV) originating from different cells are circulating in the blood of healthy subjects and their elevated numbers are found in different diseases, including cancer. This study was designed to characterise MV present in plasma of gastric cancer patients. Since majority of MV in blood are platelets-derived (PMV), plasma samples deprived of PMV were used. In comparison to control, the number of MV in patients was significantly elevated in all stages, higher in more advanced disease. Patients' MV showed an increased membrane expression of CCR6 and HER-2/neu. The proportion of MV carrying some leucocyte determinants was low and similar in patients and control. Transmission electron microscopy showed their substantial heterogeneity in size and shape. The size determined by dynamic light scattering analysis confirmed this heterogeneity. The MV size distribution in patients was broader within the range of 10-800 nm, while in control MV showed 3-mode distribution within the range of 10-400 nm. Atomic force microscopy confirmed MV size heterogeneity with implication that larger objects represented aggregates of smaller microparticles. Patients' MV exhibited increased absolute values of zeta potential, indicating a higher surface charge. Tumour markers HER-2/neu, MAGE-1, c-MET and EMMPRIN were detected both in control and patients' samples with stronger expression in the latter. Significantly higher expression of MAGE-1 and HER-2/neu mRNA was observed in individual patients. All together, it suggests that at least some MV in plasma of gastric cancer patients are tumour-derived. However, their role in cancer requires further studies.
Insights
Gastric cancer patients have significantly elevated levels of circulating microvesicles (MV), which show increased expression of tumor markers like HER-2/neu. These findings suggest some MVs in gastric cancer patients may originate from tumors.
Area of Science:
- Oncology
- Cell Biology
- Biochemistry
Background:
- Microvesicles (MVs) are cell membrane fragments circulating in blood.
- Elevated MV levels are associated with various diseases, including cancer.
- Platelet-derived MVs (PMVs) are the majority in blood.
Purpose of the Study:
- To characterize MVs in the plasma of gastric cancer patients.
- To investigate potential differences between MVs from patients and healthy controls.
- To explore the origin and characteristics of MVs in gastric cancer.
Main Methods:
- Plasma samples from gastric cancer patients and controls were analyzed after PMV depletion.
- MV characterization included quantification, surface marker expression analysis (CCR6, HER-2/neu, leukocyte determinants), size and shape analysis (TEM, DLS, AFM), zeta potential measurement, and detection of tumor markers (HER-2/neu, MAGE-1, c-MET, EMMPRIN) and mRNA.
- Statistical analysis was performed to compare patient and control groups.
Main Results:
- Gastric cancer patients exhibited significantly elevated MV numbers compared to controls, with higher levels in advanced disease stages.
- Patients' MVs showed increased membrane expression of CCR6 and HER-2/neu.
- MV size distribution was broader in patients (10-800 nm) than controls (10-400 nm), with larger objects potentially being aggregates.
- Patients' MVs had higher absolute zeta potential values, indicating increased surface charge.
- Tumor markers (HER-2/neu, MAGE-1, c-MET, EMMPRIN) were detected, with stronger expression in patients, and MAGE-1 and HER-2/neu mRNA expression was significantly higher in individual patients.
Conclusions:
- The study suggests that a portion of circulating MVs in gastric cancer patients are tumor-derived.
- Elevated MV levels and altered marker expression in gastric cancer patients warrant further investigation.
- The role of these tumor-derived MVs in the progression and pathogenesis of gastric cancer requires additional research.
