Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers.
OBJECTIVE
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.
Burleson
Kathryn M
KM
Department of Laboratory Medicine and Pathology, University of Minnesota, Minneapolis, MN 55455, USA.
Casey
Rachael C
RC
Skubitz
Keith M
KM
Pambuccian
Stephan E
SE
Oegema
Theodore R
TR
Skubitz
Amy P N
AP
D001201:Ascites / Q000473:pathology; D002448:Cell Adhesion / Q000502:physiology; D004848:Epithelium / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism / Q000473:pathology*; D016326:Extracellular Matrix Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000378:metabolism; D019012:Integrin beta1 / Q000378:metabolism; D009367:Neoplasm Staging; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*; D010529:Peritoneal Cavity / Q000473:pathology; D018874:Spheroids, Cellular / Q000473:pathology; D014407:Tumor Cells, Cultured
D016326:Extracellular Matrix Proteins; D019012:Integrin beta1; D006820:Hyaluronic Acid