Circulating tumour-derived microvesicles in plasma of gastric cancer patients
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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.
KeywordsMicrovesicles Gastric cancer Chemokine receptors Tumour markers
Atomic force microscopy
Transmission electron microscopy
This study was supported by the State Committee for Scientific Research (grant no. 2 PO5A 049 29) and by Jagiellonian University Medical College (grant no: CRSW K/ZBW/000092). We thank Dr. Barbara Urbanowicz for TEM analysis and Mrs. Irena Ruggiero for skilful technical assistance.
- 5.Baj-Krzyworzeka M, Szatanek R, Weglarczyk K, Baran J, Urbanowicz B, Branski P, Ratajczak MZ, Zembala M (2006) Tumour-derived microvesicles carry several surface determinants and mRNA of tumour cells and transfer some of these determinants to monocytes. Cancer Immunol Immunother 55:808–818CrossRefPubMedGoogle Scholar
- 6.Taylor DD, Black PH (1986) Shedding of plasma membrane fragments. Neoplastic and developmental importance. Dev Biol 3:33–57Google Scholar
- 23.Huber V, Fais S, Iero M, Lugini L, Canese P, Squarcina P, Zaccheddu A, Colone M, Arancia G, Gentile M, Seregni E, Valenti R et al (2005) Human colorectal cancer cells induce T-cell death through release of proapoptotic microvesicles: role in immune escape. Gastroenterology 128:1796–1804CrossRefPubMedGoogle Scholar
- 25.Valenti R, Huber V, Filipazzi P, Pilla L, Sovena G, Villa A, Corbelli A, Fais S, Parmiani G, Rivoltini L (2006) Human tumor-released microvesicles promote the differentiation of myeloid cells with transforming growth factor-beta-mediated suppressive activity on T lymphocytes. Cancer Res 66:9290–9298CrossRefPubMedGoogle Scholar
- 31.Sobin LH, Wittekind C (2002) TNM classification of malignant tumours, 6th edn. Wiley, HobokenGoogle Scholar
- 33.Szatanek R, Drabik G, Baran J, Kolodziejczyk P, Kulig J, Stachura J, Zembala M (2008) Detection of isolated tumour cells in the blood and bone marrow of patients with gastric cancer by combined sorting, isolation and determination of MAGE-1, -2 mRNA expression. Oncol Rep 19:1055–1060PubMedGoogle Scholar
- 45.Tadros TF (2007) General principles of colloid stability and the role of surface forces. In: Tadros TF (ed) Colloid stability part I. Viley-VCH Verlag GmbH, WeinheimGoogle Scholar
- 47.Jansa R, Sustar V, Frank M, Susanj P, Bester J, Mancek-Keber M, Krzan M, Iglic A (2008) Number of microvesicles in peripheral blood and ability of plasma to induce adhesion between phospholipid membranes in 19 patients with gastrointestinal diseases. Blood Cells Mol Dis 41:124–132CrossRefPubMedGoogle Scholar