Disaggregation and invasion of ovarian carcinoma ascites spheroids

Kathryn M. Burleson, Matthew P. Boente, Stefan E. Pambuccian, Amy P Skubitz

Research output: Contribution to journalArticle

94 Citations (Scopus)

Abstract

Background: Malignant ascites often develops in advanced stages of ovarian carcinoma, consisting of single and aggregated tumor cells, or spheroids. Spheroids have commonly been used as tumor models to study drug efficacy, and have shown resistance to some chemotherapies and radiation. However, little is known about the adhesive or invasive capabilities of spheroids, and whether this particular cellular component of the ascites can contribute to dissemination of ovarian cancer. Here, we examined the invasive ability of ascites spheroids recovered from seven ovarian carcinoma patients and one primary peritoneal carcinoma (PPC) patient. Methods: Ascites spheroids were isolated from patients, purified, and immunohistochemical analyses were performed by a pathologist to confirm diagnosis. In vitro assays were designed to quantify spheroid disaggregation on a variety of extracellular matrices and dissemination on and invasion into normal human mesothelial cell monolayers. Cell proliferation and viability were determined in each assay, and statistical significance demonstrated by the student's t-test. Results: Spheroids from all of the patients' ascites samples disaggregated on extracellular matrix components, with the PPC spheroids capable of complete disaggregation on type I collagen. Additionally, all of the ascites spheroid samples adhered to and disaggregated on live human mesothelial cell monolayers, typically without invading them. However, the PPC ascites spheroids and one ovarian carcinoma ascites spheroid sample occasionally formed invasive foci in the mesothelial cell monolayers, suggestive of a more invasive phenotype. Conclusion: We present here in vitro assays using ascites spheroids that imitate the spread of ovarian cancer in vivo. Our results suggest that systematic studies of the ascites cellular content are necessary to understand the biology of ovarian carcinoma.

Original languageEnglish (US)
Article number6
JournalJournal of Translational Medicine
Volume4
DOIs
StatePublished - Jan 24 2006

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Ascites
Monolayers
Assays
Carcinoma
Tumors
Chemotherapy
Cell proliferation
Collagen Type I
Adhesives
Cells
Students
Radiation
Ovarian Neoplasms
Extracellular Matrix
Pharmaceutical Preparations
Neoplasms
Cell Survival
Cell Proliferation
Phenotype
Drug Therapy

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Disaggregation and invasion of ovarian carcinoma ascites spheroids. / Burleson, Kathryn M.; Boente, Matthew P.; Pambuccian, Stefan E.; Skubitz, Amy P.

In: Journal of Translational Medicine, Vol. 4, 6, 24.01.2006.

Research output: Contribution to journalArticle

Burleson, Kathryn M. ; Boente, Matthew P. ; Pambuccian, Stefan E. ; Skubitz, Amy P. / Disaggregation and invasion of ovarian carcinoma ascites spheroids. In: Journal of Translational Medicine. 2006 ; Vol. 4.
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