Ovarian Carcinoma Ascites Spheroids Adhere to Extracellular Matrix Components and Mesothelial Cell Monolayers
Abstract
Objectives Ovarian carcinoma cells form multicellular aggregates, or spheroids, in the peritoneal cavity of patients with advanced disease. The current paradigm that ascites spheroids are non-adhesive leaves their contribution to ovarian carcinoma dissemination undefined. Here, spheroids obtained from ovarian carcinoma patients' ascites were characterized for their ability to adhere to molecules encountered in the peritoneal cavity, with the goal of establishing their potential to contribute to ovarian cancer spread.Methods Spheroids were recovered from the ascites fluid of 11 patients with stage III or stage IV ovarian carcinoma. Adhesion assays to extracellular matrix (ECM) proteins and human mesothelial cell monolayers were performed for each of the ascites spheroid samples. Subsequently, inhibition assays were performed to identify the cell receptors involved.Results Most ascites samples adhered moderately to fibronectin and type I collagen, with reduced adhesion to type IV collagen and laminin. Monoclonal antibodies against the beta1 integrin subunit partially inhibited this adhesion. Ascites spheroids also adhered to hyaluronan. Additionally, spheroids adhered to live, but not fixed, human mesothelial cell monolayers, and this adhesion was partially mediated by beta1 integrins.Conclusions The cellular content of the ascites fluid has often been considered non-adhesive, but our findings are the first to suggest that patient-derived ascites spheroids can adhere to mesothelial extracellular matrix via beta1 integrins, indicating that spheroids should not be ignored in the dissemination of ovarian cancer.
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OVCAR-5 spheroids plated on a collagen-I coating were observed to readily disaggregate with increasing collagen concentration, compared to laminin or collagen-IV coatings, thus highlighting its properties as a promoter of cancer cell adhesion and invasion.
“OVCAR-5 spheroids plated on a collagen-I coating, were observed to readily disaggregate with increasing collagen concentration, compared to laminin or collagen-IV coatings, thus highlighting its properties as a promoter of cancer cell adhesion and invasion (Burleson et al., 2004).”
From Three-dimensional modelling of ovarian cancer: from cell lines to organoids for discovery and personalized medicine (2022) · cites this paper as Burleson et al., 2004
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- Authors
- Burleson, K. M., Casey, R. C., Skubitz, K. M., Pambuccian, S. E., Oegema, T. R., & Skubitz, A. P. N.
- Affiliations
- University of Minnesota (US)
- Corresponding author
- Skubitz, Amy P.N
- Venue
- Gynecologic Oncology
- Publisher
- Elsevier BV
- Published
- 2004-04
- Volume
- 93
- Issue
- 1
- Pages
- 170-181
- ISSN
- 0090-8258 (ISSN-L)
- OpenAlex
- W1996604878
- Cited by
- 269
- References
- 55
- Citations by year
- 2026: 5 · 2025: 10 · 2024: 9 · 2023: 14 · 2022: 11 · 2021: 24 · 2020: 23 · 2019: 12 · 2018: 13 · 2017: 17 · 2016: 13 · 2015: 13 · 2014: 21 · 2013: 18 · 2012: 11
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Gynecologic Oncology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- University of Minnesota
- National Institutes of Health
- Topics
- Health Sciences › Medicine › Reproductive Medicine › Ovarian cancer diagnosis and treatment
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Keywords
- ovarian carcinoma, ascites, tumor spheroids, cell adhesion, extracellular matrix, mesothelial cells, beta1 integrin, fibronectin, collagen, hyaluronic acid, cancer dissemination, peritoneal carcinomatosis
- MeSH terms
- Ascites, Cell Adhesion, Epithelium, Extracellular Matrix, Female, Humans, Hyaluronic Acid, Neoplasm Staging, Ovarian Neoplasms, Peritoneal Cavity, Tumor Cells, Cultured, Extracellular Matrix Proteins, Spheroids, Cellular, Integrin beta1
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