Similar Datasets
Project description:ETS1 expression is induced by the microenvironment of ovarian metastasis and this expression allows ETS1 to activate a gene expression program involved in cell invasion and epithelial mesenchymal transision.
2018-07-24 | GSE101833 | GEO
Project description:ETS1 expression is induced by the microenvironment of ovarian metastasis and this expression allows ETS1 to activate a gene expression program involved in cell invasion and epithelial mesenchymal transision.
2018-07-24 | GSE101832 | GEO
Project description:ETS1 induction by the omental microenvironment promotes ovarian cancer metastasis
| PRJNA395678 | ENA
Project description:Background: Tumor metastasis is the major challenge for ovarian cancer treatment. Cancer-associated fibroblasts (CAFs), a major component existing in tumor microenvironment, can secrete several cytokines to interact with cancer epithelial cells, and promote cancer metastasis. Stanniocalcin 1 (STC1), a secretory glycoprotein hormone, has been proven to be an important factor in ovarian tumorigenesis. Methods: In this study, we focused on the functional role of STC1 in ovarian cancer microenvironment, investigated STC1's effects on the proliferation and metastasis of ovarian cancer cells, and explored the molecular mechanism underlying STC1-mediated cancer metastasis. Results: By analyzing the GEO dataset and examined STC1 expression in CAFs isolated from ovarian cancer patients, we found that expression of STC1 was higher in ovarian cancer stroma and CAFs than in the normal ovarian stroma and normal fibroblasts (NFs). Addition of recombinant human STC1 (rhSTC1) promoted cell proliferation and metastasis in ovarian cancer, while adoption of STC1 neutralizing antibody (STC1 Ab) abolished the effects. Furthermore, our results revealed that STC1 promoted the phosphorylation of Akt (Ser473), and upregulated several epithelial-mesenchymal transition (EMT) markers including fibronectin，vimentin and slug. In addition, we demonstrated that STC1 in tumor microenvironment could mediate the conversion of NFs to CAFs. Conclusion: Taken together, the study results suggested the crucial role of STC1 in tumor environment on the metastasis of ovarian cancer.
| S-EPMC6489642 | biostudies-literature
Project description:Ovarian cancer can metastasize to the omentum, which is associated with a complex tumor microenvironment. Omental stromal cells facilitate ovarian cancer colonization by secreting cytokines and growth factors. Improved understanding of the tumor supportive functions of specific cell populations in the omentum could identify strategies to prevent and treat ovarian cancer metastasis. Here, we showed that omental preadipocytes enhance the tumor initiation capacity of ovarian cancer cells. Secreted factors from preadipocytes supported cancer cell viability during nutrient and isolation stress and enabled prolonged proliferation. Co-culturing with pre-adipocytes led to upregulation of genes involved in extracellular matrix (ECM) organization, cellular response to stress, and regulation of insulin-like growth factor (IGF) signaling in ovarian cancer cells. IGF-1 induced ECM genes and increased alternative NF-κB signaling by activating RelB. Inhibiting the IGF-1 receptor (IGF1R) initially increased tumor omental adhesion but decreased growth of established preadipocyte-induced subcutaneous tumors as well as established intraperitoneal tumors. Together, this study shows that omental preadipocytes support ovarian cancer progression, which has implications for targeting metastasis.
| S-EPMC11217736 | biostudies-literature
Project description:Ovarian cancer (OC) is the most lethal gynecological malignancy, with aggressive metastatic disease responsible for the majority of OC-related deaths. In particular, OC tumors preferentially metastasize to and proliferate rapidly in the omentum. Here, we show that metastatic OC cells experience increased oxidative stress in the omental microenvironment. Metabolic reprogramming, including upregulation of the pentose phosphate pathway (PPP), a key cellular redox homeostasis mechanism, allows OC cells to compensate for this challenge. Inhibition of glucose-6-phosphate dehydrogenase (G6PD), the rate-limiting enzyme of the PPP, reduces tumor burden in pre-clinical models of OC, suggesting that this adaptive metabolic dependency is important for OC omental metastasis.
| S-EPMC9534522 | biostudies-literature
Project description:The primary site of metastasis for epithelial ovarian cancer (EOC) is the peritoneum, and it occurs through a multistep process that begins with adhesive contacts between cancer cells and mesothelial cells. Despite evidence that Notch signaling has a role in ovarian cancer, it is unclear how exactly it contributes to ovarian cancer omental metastasis, as well as the cellular dynamics and intrinsic pathways that drive this tropism. Here we show that tumor cells produced the Notch ligand Jagged2 is a clinically and functionally critical mediator of ovarian cancer omental metastasis by activating the Notch signaling in single-layered omental mesothelial cells. In turn, Jagged2 promotes tumor growth and therapeutic resistance by stimulating IL-6 release from mesothelial cells. Additionally, Jagged2 is a potent downstream mediator of the omental metastasis cytokine TGF-β that is released during omental destruction. Importantly, therapeutic inhibition of Jagged2-mediated omental metastasis was significantly improved by directly disrupting the Notch pathway in omental mesothelial cells. These findings highlight the key role of Jagged2 to the functional interplay between the TGF-β and the Notch signaling pathways during the metastatic process of ovarian cancer cells to the omentum and identify the Notch signaling molecule as a precision therapeutic target for ovarian cancer metastasis.
| S-EPMC10995149 | biostudies-literature
Project description:Ovarian cancer is an insidious and aggressive disease of older women, typically undiscovered before peritoneal metastasis due to its asymptomatic nature and lack of early detection tools. Epidemiologic studies suggest that child-bearing (parity) is associated with decreased ovarian cancer risk, although the molecular mechanisms responsible for this phenomenon have not been delineated. Ovarian cancer preferentially metastasizes to the omental fat band (OFB), a secondary lymphoid organ that aids in filtration of the peritoneal serous fluid (PSF) and helps combat peritoneal infections. In the present study, we assessed how parity and age impact the immune compositional profile in the OFB of mice, both in the homeostatic state and as a consequence of peritoneal implantation of ovarian cancer. Using fluorescence-activated cell sorting analysis and quantitative real-time PCR, we found that parity was associated with a significant reduction in omental monocytic subsets and B1-B lymphocytes, correlating with reduced homeostatic expression levels of key chemoattractants and polarization factors (Ccl1, Ccl2, Arg1, and Cxcl13). Of note, parous animals exhibited significantly reduced tumor burden following intraperitoneal implantation compared with nulliparous animals. This was associated with a reduction in tumor-associated neutrophils and macrophages, as well as in the expression levels of their chemoattractants (Cxcl1 and Cxcl5) in the OFB and PSF. These findings define a preexisting "parity-associated microenvironmental niche" in the OFB that is refractory to metastatic tumor seeding and outgrowth. Future studies designed to manipulate this niche may provide a novel means to mitigate peritoneal dissemination of ovarian cancer.
| S-EPMC3836366 | biostudies-literature
Project description:This SuperSeries is composed of the SubSeries listed below.
2023-12-19 | GSE228805 | GEO
Project description:IntroductionOvarian and other peritoneal cancers have a strong tendency to metastasize into the surrounding adipose tissue. This study describes an effect of the adipose microenvironment on upregulation of sialic acid-containing glycans in ovarian cancer (OC). Heterogeneous populations of glycosylated OC tumors converged to a highly sialylated cell state that regulates tumorigenesis in an immune-dependent manner.MethodsWe modeled the adipose microenvironment by conditioning growth media with human patient-derived adipose tissue. OC cell lines grown in the presence vs. absence of adipose conditioned media (ACM) were characterized by transcriptomics, western blotting, and chemical biology glycan labeling methods. Fluorescence-activated cell sorting was used to separate adipose-driven upregulation of hypersialylated ("SNA-high") vs. hyposialylated ("SNA-low") OC subpopulations. The two subpopulations were characterized by further transcriptomic and quantitative polymerase chain reaction analyses, then injected into a syngeneic mouse model. Immune system involvement was implicated using wild type and athymic nude mice with a primary endpoint of overall survival.ResultsAdipose conditioning resulted in upregulation of sialyltransferases ST3GAL1, ST6GAL1, ST6GALNAC3, and ST8Sia1. In culture, OC cells displayed two distinct sialylated subpopulations that were stable for up to 9 passages, suggesting inherent heterogeneity in sialylation that is maintained throughout cell division and media changes. OC tumors that implanted in the omental adipose tissue exclusively reprogrammed to the highly sialylated subpopulation. In wild type C57BL/6 mice, only the hypersialylated SNA-high subpopulation implanted in the adipose, whereas the hyposialylated SNA-low subpopulation failed to be tumorigenic (p=0.023, n=5). In the single case where SNA-low established a tumor, post-mortem analysis revealed reprogramming of the tumor to the SNA-high state in vivo. In athymic nude mice, both subpopulations rapidly formed tumors, implicating a role of the adaptive immune system.ConclusionsThese findings suggest a model of glycan-dependent tumor evolution wherein the adipose microenvironment reprograms OC to a tumorigenic state that resists the adaptive immune system. Mechanistically, adipose factors upregulate sialyltransferases. To our knowledge, this is the first demonstration of the effect of adipose microenvironment on OC tumor sialylation. Our results set the stage for translational applications targeting sialic acid pathways in OC and other peritoneal cancer tumorigenesis and metastasis.
| S-EPMC11299042 | biostudies-literature