Modeling the Early Steps of Ovarian Cancer Dissemination in an Organotypic Culture of the Human Peritoneal Cavity

2021 ◽  
pp. 75-94
Author(s):  
Peter C. Hart ◽  
Preety Bajwa ◽  
Hilary A. Kenny
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Organotypic Culture ◽  
Cancer Dissemination

scholarly journals Selectins: An Important Family of Glycan-Binding Cell Adhesion Molecules in Ovarian Cancer

Cancers ◽  
2020 ◽  
Vol 12 (8) ◽  
pp. 2238
Author(s):  
Ayon A. Hassan ◽  
Margarita Artemenko ◽  
Maggie K.S. Tang ◽  
Alice S.T. Wong
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Cell Interaction ◽  
Gynecological Malignancy ◽  
Selectin Ligand ◽  
Cancer Dissemination ◽  
Tumor Types ◽  
Potential Therapeutic Intervention ◽  
Binding Cell

Ovarian cancer is the most lethal gynecological malignancy worldwide. Unlike most other tumor types that metastasize via the vasculature, ovarian cancer metastasizes predominantly via the transcoelomic route within the peritoneal cavity. As cancer metastasis accounts for the majority of deaths, there is an urge to better understand its determinants. In the peritoneal cavity, tumor-mesothelial adhesion is an important step for cancer dissemination. Selectins are glycan-binding molecules that facilitate early steps of this adhesion cascade by mediating heterotypic cell-cell interaction under hydrodynamic flow. Here, we review the function and regulation of selectins in peritoneal carcinomatosis of ovarian cancer, and highlight how dysregulation of selectin ligand biogenesis affects disease outcome. Further, we will introduce the latest tools in studying selectin-glycan interaction. Finally, an overview of potential therapeutic intervention points that may lead to the development of efficacious therapies for ovarian cancer is provided.

Cytotoxic lymphocytes, interferon, and tumor rejection in the peritoneal cavity of a murine ovarian cancer model using immunotherapy with biologic response modifiers

1983 ◽  
Vol 15 (1) ◽  
pp. 136
Author(s):  
Jonathan S. Berek ◽  
Neville F. Hacker ◽  
Jacob Zighelboim ◽  
Alan Lichtenstein ◽  
Reba Knox ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Peritoneal Cavity ◽  
Tumor Rejection ◽  
Cytotoxic Lymphocytes ◽  
Cancer Model ◽  
Biologic Response

Characterization of an intraperitoneal ovarian cancer xenograft model in nude rats using noninvasive microPET imaging

2007 ◽  
Vol 17 (2) ◽  
pp. 407-417 ◽  
Author(s):  
C. L. Zavaleta ◽  
W. T. Phillips ◽  
Y. C. Bradley ◽  
L. M. McMANUS ◽  
P. A. Jerabek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Lymph Nodes ◽  
Peritoneal Cavity ◽  
Imaging Modality ◽  
Xenograft Model ◽  
Tumor Model ◽  
Fdg Uptake ◽  
Tumor Bearing ◽  
Nude Rats ◽  
Biodistribution Data

MicroPET is a noninvasive imaging modality that can potentially track tumor development in nude rats using the radiotracer fluorine 18-fluorodeoxyglucose (18F-FDG). Our goal was to determine whether microPET, as opposed to more invasive techniques, could be used to noninvasively monitor the development of ovarian cancer in the peritoneal cavity of nude rats for monitoring treatment response in future studies. Female nude rats were inoculated intraperitoneally with 36 million NIH:OVCAR-3 cells. Imaging was carried out at 2, 4, 6, or 8 weeks postinoculation. Each rat was fasted overnight and intravenously injected with 11.1 MBq (300 μCi) of 18F-FDG in 0.2 mL of saline. Thirty minutes following injection, the rats were placed in the microPET and scanned for 30 min. After imaging, rats were euthanized for ascites and tissue collection for biodistribution and histopathologic correlation. Standard uptake values (SUVs) of 18F-FDG within the peritoneal cavity were also calculated from regions of interest analysis of the microPET images. MicroPET images showed diffuse increased uptake of 18F-FDG throughout the peritoneal cavity of tumor rats (mean SUV = 4.64) compared with control rats (mean SUV = 1.03). Ascites gathered from tumor-bearing rats had increased 18F-FDG uptake as opposed to the peritoneal fluid collected from control rats. Biodistribution data revealed that the percent injected dose per gram (% ID/g) was significantly higher in tumor-bearing rats (6.29%) than in control rats (0.59%) in the peritoneal lymph nodes. Pathology verified that these lymph nodes were more reactive in tumor-bearing rats. By 6 weeks, some rats developed solid masses within the peritoneum, which could be detected on microPET images and confirmed as tumor by histopathology. 18F-FDG uptake in these tumors at necropsy was 2.83% ID/g. These results correlate with previous invasive laparoscopic studies of the same tumor model and demonstrate that microPET using 18F-FDG is a promising noninvasive tool to localize and follow tumor growth in an intraperitoneal ovarian cancer model.

scholarly journals Lysophosphatidic Acid Disrupts Junctional Integrity and Epithelial Cohesion in Ovarian Cancer Cells

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Yueying Liu ◽  
Rebecca Burkhalter ◽  
Jaime Symowicz ◽  
Kim Chaffin ◽  
Shawn Ellerbroek ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Lysophosphatidic Acid ◽  
Time Dependent ◽  
Ovarian Cancer Cells ◽  
Ectodomain Shedding ◽  
Lpa Receptor ◽  
Multicellular Aggregates ◽  
Cancer Dissemination ◽  
E Cadherin

Ovarian cancer metastasizes via exfoliation of free-floating cells and multicellular aggregates from the primary tumor to the peritoneal cavity. A key event in EOC metastasis is disruption of cell-cell contacts via modulation of intercellular junctional components including cadherins. Ascites is rich in lysophosphatidic acid (LPA), a bioactive lipid that may promote early events in ovarian cancer dissemination. The objective of this paper was to assess the effect of LPA on E-cadherin junctional integrity. We report a loss of junctional E-cadherin in OVCAR3, OVCA429, and OVCA433 cells exposed to LPA. LPA-induced loss of E-cadherin was concentration and time dependent. LPA increased MMP-9 expression and promoted MMP-9-catalyzed E-cadherin ectodomain shedding. Blocking LPA receptor signaling inhibited MMP-9 expression and restored junctional E-cadherin staining. LPA-treated cells demonstrated a significant decrease in epithelial cohesion. Together these data support a model wherein LPA induces MMP-9 expression and MMP-9-catalyzed E-cadherin ectodomain shedding, resulting in loss of E-cadherin junctional integrity and epithelial cohesion, facilitating metastatic dissemination of ovarian cancer cells.

scholarly journals Pathogenesis of malignant ascites in ovarian cancer patients

2004 ◽  
Vol 12 (2) ◽  
pp. 115-118 ◽  
Author(s):  
Zorica Stanojevic ◽  
Gorana Rancic ◽  
Stojan Radic ◽  
Natasa Potic-Zecevic ◽  
Biljana Djordjevic ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Patients ◽  
Peritoneal Cavity ◽  
Malignant Disease ◽  
Prognostic Significance ◽  
Malignant Ascites ◽  
Malignant Cells ◽  
Stage Disease ◽  
New Treatment ◽  
End Stage

Peritonitis carcinomatosa, indicating the presence of malignant cells in the peritoneal cavity, is a well- known complication of malignant disease. The collection of intraperitoneal fluid in a patient with ovarian cancer is most likely due to intraperitoneal spread of disease. The recognition of small quantities of intraperitoneal fluid may have staging and prognostic significance, while symptomatic large collections may reflect end-stage disease, which permits only palliative therapeutic options. In this paper we dis- cussed the pathogenesis of malignant ascites in ovarian cancer patients and suggested potential new treatment approaches.

scholarly journals A systematic CRISPR screen reveals an IL-20/IL20RA-mediated immune crosstalk to prevent the ovarian cancer metastasis

eLife ◽  
2021 ◽  
Vol 10 ◽  
Author(s):  
Jia Li ◽  
Xuan Qin ◽  
Jie Shi ◽  
Xiaoshuang Wang ◽  
Tong Li ◽  
...  
Keyword(s):  
Ovarian Cancer ◽  
Cancer Cells ◽  
Peritoneal Cavity ◽  
Cancer Metastasis ◽  
Immune Surveillance ◽  
Mesothelial Cells ◽  
Downstream Signaling ◽  
Key Factor ◽  
Crispr Screen

Transcoelomic spread of cancer cells across the peritoneal cavity occurs in most initially diagnosed ovarian cancer (OC) patients and accounts for most cancer-related death. However, how OC cells interact with peritoneal stromal cells to evade the immune surveillance remains largely unexplored. Here, through an in vivo genome-wide CRISPR/Cas9 screen, we identified IL20RA, which decreased dramatically in OC patients during peritoneal metastasis, as a key factor preventing the transcoelomic metastasis of OC. Reconstitution of IL20RA in highly metastatic OC cells greatly suppresses the transcoelomic metastasis. OC cells, when disseminate into the peritoneal cavity, greatly induce peritoneum mesothelial cells to express IL-20 and IL-24, which in turn activate the IL20RA downstream signaling in OC cells to produce mature IL-18, eventually resulting in the polarization of macrophages into the M1-like subtype to clear the cancer cells. Thus, we show an IL-20/IL20RA-mediated crosstalk between OC and mesothelial cells that supports a metastasis-repressing immune microenvironment.

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