Dataset Information

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

ABSTRACT: Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, substantial mesothelial-to-mesenchymal transition (MMT) and released EVs that both directed tumor invasion and caused reprogramming of secretory profiles by increasing TGF-β1 and uPA/uPAR expression and MMP-2/9 activation in tumor cells. Notably, the EVs released by tumor cells induced apoptosis by activating caspase-3, peritoneal MC senescence, and MMT, thereby augmenting the tumor-promoting potential of these cells in the peritoneal cavity. By using pantoprazole, we reduced the biogenesis of EVs and their pro-tumor functions. In conclusion, our findings provided evidence of underlying mechanisms of CRC dissemination driven by the interaction of peritoneal MCs and tumor cells via the EVs released in the peritoneal cavity, which may have important implications for the clinical management of patients.

SUBMITTER: Serrati S

PROVIDER: S-EPMC8161093 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

Serratì Simona S Porcelli Letizia L Fragassi Francesco F Garofoli Marianna M Di Fonte Roberta R Fucci Livia L Iacobazzi Rosa Maria RM Palazzo Antonio A Margheri Francesca F Cristiani Grazia G Albano Anna A De Luca Raffaele R Altomare Donato Francesco DF Simone Michele M Azzariti Amalia A

Cancers 20210520 10

Advanced colorectal cancer (CRC) is highly metastatic and often results in peritoneal dissemination. The extracellular vesicles (EVs) released by cancer cells in the microenvironment are important mediators of tumor metastasis. We investigated the contribution of EV-mediated interaction between peritoneal mesothelial cells (MCs) and CRC cells in generating a pro-metastatic environment in the peritoneal cavity. Peritoneal MCs isolated from peritoneal lavage fluids displayed high CD44 expression, ...[more]

PMID: 34065529

Similar Datasets

Project description:BackgroundMetastasis is the key cause of death in ovarian cancer patients. To figure out the biological nature of cancer metastasis is essential for developing effective targeted therapy. Here we investigate how long non-coding RNA (lncRNA) SPOCD1-AS from ovarian cancer extracellular vesicles (EVs) remodel mesothelial cells through a mesothelial-to-mesenchymal transition (MMT) manner and facilitate peritoneal metastasis.MethodsEVs purified from ovarian cancer cells and ascites of patients were applied to mesothelial cells. The MMT process of mesothelial cells was assessed by morphology observation, western blot analysis, migration assay and adhesion assay. Altered lncRNAs of EV-treated mesothelial cells were screened by RNA sequencing and identified by qRT-PCR. SPOCD1-AS was overexpressed or silenced by overexpression lentivirus or shRNA, respectively. RNA pull-down and RNA immunoprecipitation assays were conducted to reveal the mechanism by which SPOCD1-AS remodeled mesothelial cells. Interfering peptides were synthesized and applied. Ovarian cancer orthotopic implantation mouse model was established in vivo.ResultsWe found that ovarian cancer-secreted EVs could be taken into recipient mesothelial cells, induce the MMT phenotype and enhance cancer cell adhesion to mesothelial cells. Furthermore, SPOCD1-AS embedded in ovarian cancer-secreted EVs was transmitted to mesothelial cells to induce the MMT process and facilitate peritoneal colonization in vitro and in vivo. SPOCD1-AS induced the MMT process of mesothelial cells via interacting with G3BP1 protein. Additionally, G3BP1 interfering peptide based on the F380/F382 residues was able to block SPOCD1-AS/G3BP1 interaction, inhibit the MMT phenotype of mesothelial cells, and diminish peritoneal metastasis in vivo.ConclusionsOur findings elucidate the mechanism associated with EVs and their cargos in ovarian cancer peritoneal metastasis and may provide a potential approach for metastatic ovarian cancer therapeutics.

Project description:BackgroundTo investigate the effects and mechanism of high concentration glucose (HG), exogenous hydrogen peroxide (H2O2), and antioxidants on the cell growth (cell proliferation) of human peritoneal mesothelial cells (HPMCs).MethodsAll tests were conducted on cultured HPMCs (HMrSV5) in vitro. Various concentrations of glucose (0.1%, 1.35%, and 3.86%), H2O2 (0.5 and 0.1 mmol/L), and antioxidants (pyruvate and catalase) were used in cell culture. Moreover, in order to study the interaction between these factors, HG and H2O2, HG and antioxidants, HG, H2O2, and antioxidants, were used respectively. After 12-24 h, phase-contrast microscopy was used to examine the morphological changes of HPMCs. DNA synthesis was detected by 3H-thymidine incorporation to measure cell proliferation, and flow cytometry was used to evaluate the proportion of cells in G1 phase. Furthermore, semiquantitative reverse-transcription polymerase chain reaction (RT-PCR) was utilized to determine the mRNA expression of p21Waf1 and p27Kip1 [cyclin-dependent kinase inhibitors (CKIs)], while immunocytochemistry (ICC) and Western blotting were employed to measure the protein expression of p21Waf1 and p27Kip1.ResultsHG or low-dose exogenous H2O2 resulted in hypertrophy and senescence of HPMCs, resulting in similar morphological changes. Both HG and exogenous H2O2 (0.5 mmol/L) inhibited the proliferation of HPMCs and led to G1 phase arrest of HPMCs. The proportion of cells in G1 phase increased. Moreover, HG enhanced the toxic effects of exogenous H2O2. Both HG and exogenous H2O2 increased the expression of p21Waf1 and p27Kip1 . The addition of an antioxidant in HG medium arrested cells in the G1 phase and improved the inhibited cell proliferation.ConclusionsBoth HG and exogenous H2O2 treatments can induce growth inhibition of HPMCs by arresting cell cycle progression, which is partially due to the increased expression of p21Waf1 and p27Kip1 . Thus, the effects of HG might be associated with endogenous reactive oxygen species (ROS), and it might be beneficial to use antioxidants in peritoneal dialysis (PD).

Dataset Information

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

Publications

The Interaction between Reactive Peritoneal Mesothelial Cells and Tumor Cells via Extracellular Vesicles Facilitates Colorectal Cancer Dissemination.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets