Ovarian carcinoma ascites spheroids adhere to extracellular matrix components and mesothelial cell monolayers

Kathryn M. Burleson, Rachael C. Casey, Keith M. Skubitz, Stephan E. Pambuccian, Theodore R. Oegema, Amy P.N. Skubitz

Research output: Contribution to journalArticlepeer-review

227 Scopus citations

Abstract

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 β1 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 β1 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 β1 integrins, indicating that spheroids should not be ignored in the dissemination of ovarian cancer.

Original languageEnglish (US)
Pages (from-to)170-181
Number of pages12
JournalGynecologic oncology
Volume93
Issue number1
DOIs
StatePublished - Apr 2004

Bibliographical note

Funding Information:
We thank Dr. James McCarthy for providing fibronectin, Dr. Leo Furcht for providing the mAb P5D2 against the β1 integrin subunit, and Dr. Judah Folkman for providing the NIH:OVCAR5 cell line. We thank Diane Rauch and Sarah Bowell of the Tissue Procurement Facility of the University of Minnesota for their assistance in collecting and processing the ascites samples. This project was supported by grants from the Minnesota Medical Foundation, the Office of the Dean of the Graduate School of the University of Minnesota, the Minnesota Ovarian Cancer Alliance, and the Department of the Army (DA/DAMD17-99-1-9564). The content of the information presented in this manuscript does not necessarily reflect the position of the government.

Keywords

  • Cell adhesion molecules
  • Extracellular matrix
  • Integrins
  • Ovarian carcinoma
  • Spheroids

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