Interactions of tumour-derived micro(nano)vesicles with human gastric cancer cells

Abstract

BackgroundTumour cells release membrane micro(nano)fragments called tumour-derived microvesicles (TMV) that are believed to play an important role in cancer progression. TMV suppress/modify antitumour response of the host, but there is also some evidence for their direct interaction with cancer cells. In cancer patients TMV are present in body fluid and tumour microenvironment. The present study aimed at characterization of whole types/subpopulations, but not only exosomes, of TMV from newly established gastric cancer cell line (called GC1415) and to define their interactions with autologous cells.MethodsTMV were isolated from cell cultures supernatants by centrifugation at 50,000×g and their phenotype was determined by flow cytometry. The size of TMV was analysed by dynamic light scattering and nanoparticle tracking analysis, while morphology by transmission electron microscopy and atomic force microscopy. Interactions of TMV with cancer cells were visualized using fluorescence-activated cell sorter, confocal and atomic force microscopy, biological effects by xenografts in NOD SCID mice.ResultsIsolated TMV showed expression of CD44H, CD44v6 (hyaluronian receptors), CCR6 (chemokine receptor) and HER-2/neu molecules, exhibited different shapes and sizes (range 60–900 nm, highest frequency of particles with size range of 80–120 nm). TMV attached to autologous cancer cells within 2 h and then were internalized by them at 24 h. CD44H, CD44v6 and CCR6 molecules may play a role in attachment of TMV to cancer cells, while HER-2 associated with CD24 be involved in promoting cancer cells growth. Pre-exposure of cancer cells to TMV resulted in enhancement of tumour growth and cancer cell-induced angiogenesis in NOD SCID mice model.ConclusionsTMV interact directly with cancer cells serving as macro-messengers and molecular cargo transfer between gastric cancer cells resulting in enhancement of tumour growth. TMV should be considered in future as target of anticancer therapy.

YB-1 transferred by gastric cancer exosomes promotes angiogenesis via enhancing the expression of angiogenic factors in vascular endothelial cells

“…Although GC-derived exosomes have been largely studied since the first characterization decades ago [20], the publications on the regulation of GC angiogenesis are limited. So far, a few of cargoes including CD44, CCR6, HER-2/neu [21] and several cytokines [22] were identified in GC-derived exosomes, and miR-130a/C-MYB [23], miR-135b/FOXO1 [24], miR-155/FOXO3 [25] and HGF [26] were, respectively, uncovered to be potential signals for exosome-HUVEC interactions. Given that the complex compositions including receptors, transcription factors, enzymes, extracellular matrix proteins, lipids, nucleic acids (DNA, mRNA, and miRNA) constitute exosomes, far further declarations on the complex working mechanisms of exosomes in GC angiogenesis are needed.…”

Extracellular vesicles from oral squamous carcinoma cells display pro‐ and anti‐angiogenic properties

“…It has been recently shown that vesicles obtained from gastric cancer cells increase angiogenesis and tumor burden in mice (Stec et al., ). EVs derived from colorectal carcinoma cells carrying miR‐1246 induce angiogenesis by the activation of SMAD cascade (Yamada et al., ), and EVs derived from renal carcinoma cells expressing CD105, a mesenchymal stem cell marker, not only collaborate with the activation of the angiogenic switch, but also guide tumor growth and metastatic spread (Grange et al., ).…”

The roles of extracellular vesicles in gastric cancer development, microenvironment, anti-cancer drug resistance, and therapy

“…In cancer patients, EVs located in body fluid and tumor microenvironment to effect cancer progression. They could directly interact with autologous cancer cells within 2 h and then were internalized by them at 24 h as messengers transfer between GC cells to enhance tumor growth have been proved [7]. The cancer-derived EVs' signature distinguishes them from normal cell secreted EVs.…”