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Title:
Gastric cancer exosomes contribute to the field cancerization of gastric epithelial cells surrounding gastric cancer | Gastric Cancer
Description:
Background A dynamic molecular interaction between cancer and the surrounding normal cells is mediated through exosomes. We investigated whether exosomes derived from gastric cancer cells affected the fate of the surrounding gastric epithelial cells. Methods We analyzed the cell viability and immortalization of primary normal stomach epithelial cells (PNSECs) after treatment with exosomes derived from AGS gastric cancer cells and/or H. pylori CagA. Cell proliferation and apoptosis were analyzed by BrdU incorporation, flow-cytometry, and colony formation assays. We examined telomere length, expression and activity of telomerase, and expression of telomere-related genes in PNSECs treated with cancer exosomes, and in 60 gastric cancer and corresponding mucosal tissues. The differentially expressed genes and transcriptional regulation of telomere-related genes were verified using real-time qPCR and ChIP analyses, respectively. Results Gastric cancer exosomes increased cell viability and the population-doubling levels but inhibited the cellular senescence and apoptosis of PNSECs. The internalization of cancer exosomes in PNSECs dramatically increased the number of surviving colonies and induced a multilayer growth and invasion into the scaffold. Treatment of PNSECs with cancer exosomes markedly increased the expression and activity of telomerase and the T/S ratio and regulated the expression of the telomere-associated genes, heat-shock genes, and hedgehog genes. Compared to gastric mucosae, gastric cancer showed increased hTERT expression, which was positively correlated with telomere length. Interestingly, seven (46.7%) of 15 non-cancerous gastric mucosae demonstrated strong telomerase activity. Conclusion These results suggest that gastric cancer exosomes induced the transformation and field cancerization of the surrounding non-cancerous gastric epithelial cells.
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ras/raf/mek/erk signaling pathway sa-Ξ²-gal-positive cells won sang park sa-Ξ²-gal-positivity sa-Ξ²-gal-positive sa-Ξ²-gal activity key inflammation-related players cumulative population-doubling level amp-activated protein kinase comprehensive high-throughput analyses cancer-primed cell population byung joon choi telomerase-positive gastric cancers rapid population-doubling times exosomal mir-27a derived cancer exosome-treated cells rapid population-doubling time diffuse-type gastric cancer secreted larger amounts dynamic molecular interaction national research foundation lkb1/ampk signaling pathway tumor exosome-mediated promotion article yoon gastric epithelial cells discover anticancer compounds surrounding gastric mucosae apoptotic cell death neoplastic gastric mucosae hh/gli axis contributes cancer exosome-treated pnseccaga promote gastric carcinogenesis human epithelial cells mapk/erk activation exosome uptake inhibitors cancer exosome-treated pnsecmock cancer exosome-treated pnsecs privacy choices/manage cookies cancerous gastric mucosae human gastric cancer surrounding normal cells drug resistance gastric cancer cells spemβ+βim expressing cdx2 full size image helicobacter pylori induces human breast cancer human cancer cells mapk/erk pathways [7 breast cancer cells
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headline:Gastric cancer exosomes contribute to the field cancerization of gastric epithelial cells surrounding gastric cancer
description:A dynamic molecular interaction between cancer and the surrounding normal cells is mediated through exosomes. We investigated whether exosomes derived from gastric cancer cells affected the fate of the surrounding gastric epithelial cells. We analyzed the cell viability and immortalization of primary normal stomach epithelial cells (PNSECs) after treatment with exosomes derived from AGS gastric cancer cells and/or H. pylori CagA. Cell proliferation and apoptosis were analyzed by BrdU incorporation, flow-cytometry, and colony formation assays. We examined telomere length, expression and activity of telomerase, and expression of telomere-related genes in PNSECs treated with cancer exosomes, and in 60 gastric cancer and corresponding mucosal tissues. The differentially expressed genes and transcriptional regulation of telomere-related genes were verified using real-time qPCR and ChIP analyses, respectively. Gastric cancer exosomes increased cell viability and the population-doubling levels but inhibited the cellular senescence and apoptosis of PNSECs. The internalization of cancer exosomes in PNSECs dramatically increased the number of surviving colonies and induced a multilayer growth and invasion into the scaffold. Treatment of PNSECs with cancer exosomes markedly increased the expression and activity of telomerase and the T/S ratio and regulated the expression of the telomere-associated genes, heat-shock genes, and hedgehog genes. Compared to gastric mucosae, gastric cancer showed increased hTERT expression, which was positively correlated with telomere length. Interestingly, seven (46.7%) of 15 non-cancerous gastric mucosae demonstrated strong telomerase activity. These results suggest that gastric cancer exosomes induced the transformation and field cancerization of the surrounding non-cancerous gastric epithelial cells.
datePublished:2022-01-07T00:00:00Z
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Gastric epithelium
Exosomes
Telomeres
Immortalization
Surgical Oncology
Oncology
Abdominal Surgery
Gastroenterology
Cancer Research
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headline:Gastric cancer exosomes contribute to the field cancerization of gastric epithelial cells surrounding gastric cancer
description:A dynamic molecular interaction between cancer and the surrounding normal cells is mediated through exosomes. We investigated whether exosomes derived from gastric cancer cells affected the fate of the surrounding gastric epithelial cells. We analyzed the cell viability and immortalization of primary normal stomach epithelial cells (PNSECs) after treatment with exosomes derived from AGS gastric cancer cells and/or H. pylori CagA. Cell proliferation and apoptosis were analyzed by BrdU incorporation, flow-cytometry, and colony formation assays. We examined telomere length, expression and activity of telomerase, and expression of telomere-related genes in PNSECs treated with cancer exosomes, and in 60 gastric cancer and corresponding mucosal tissues. The differentially expressed genes and transcriptional regulation of telomere-related genes were verified using real-time qPCR and ChIP analyses, respectively. Gastric cancer exosomes increased cell viability and the population-doubling levels but inhibited the cellular senescence and apoptosis of PNSECs. The internalization of cancer exosomes in PNSECs dramatically increased the number of surviving colonies and induced a multilayer growth and invasion into the scaffold. Treatment of PNSECs with cancer exosomes markedly increased the expression and activity of telomerase and the T/S ratio and regulated the expression of the telomere-associated genes, heat-shock genes, and hedgehog genes. Compared to gastric mucosae, gastric cancer showed increased hTERT expression, which was positively correlated with telomere length. Interestingly, seven (46.7%) of 15 non-cancerous gastric mucosae demonstrated strong telomerase activity. These results suggest that gastric cancer exosomes induced the transformation and field cancerization of the surrounding non-cancerous gastric epithelial cells.
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Gastric epithelium
Exosomes
Telomeres
Immortalization
Surgical Oncology
Oncology
Abdominal Surgery
Gastroenterology
Cancer Research
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