Abstract
BackgroundAt least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements. The components of ascites and their effects on the tumor cell microenvironment remain poorly understood. This study aimed to isolate and characterize stromal progenitor cells from the ascites of patients with epithelial ovarian adenocarcinoma (EOA).MethodsSeventeen ascitic fluid samples and 7 fresh tissue samples were collected from 16 patients with EOA. The ascites samples were then cultured in vitro in varying conditions. Flow cytometry and immunocytochemistry were used to isolate and characterize 2 cell populations with different morphologies (epithelial type and mesenchymal type) deriving from the ascites samples. The in vitro cell culture model was established using conditional culture medium.ResultsThe doubling times of the epithelial type and mesenchymal type cells were 36 h and 48 h, respectively, indicating faster growth of the epithelial type cells compared to the mesenchymal type cells. Cultured in vitro, these ascitic cells displayed the potential for self-renewal and long-term proliferation, and expressed the typical cancer stem/progenitor cell markers CD44high, CD24low, and AC133+. These cells also demonstrated high BMP-2, BMP4, TGF-β, Rex-1, and AC133 early gene expression, and expressed EGFR, integrin α2β1, CD146, and Flt-4, which are highly associated with tumorigenesis and metastasis. The epithelial type cells demonstrated higher cytokeratin 18 and E-cadherin expression than the mesenchymal type cells. The mesenchymal type cells, in contrast, demonstrated higher AC133, CD73, CD105, CD117, EGFR, integrin α2β1, and CD146 surface marker expression than the epithelial type cells.ConclusionThe established culture system provides an in vitro model for the selection of drugs that target cancer-associated stromal progenitor cells, and for the development of ovarian cancer treatments.
Highlights
At least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements
Of the 17 ascitic fluid samples included, 12 were from patients diagnosed with ovarian serous adenocarcinoma (OSA), 3 were from patients with ovarian clear cell adenocarcinoma (OCCA), and 2 were from patients with ovarian mucinous borderline tumor (OMBT)
In compare to the mesenchymal stromal cells (HOTC) of normal ovarian tissue, we have shown that mesenchymal like cancer tumor fibroblasts (HOCTC) sprouting from ovarian cancer tissue expressed higher levels of BMP2, BMP4 and TGF-b, which are highly associated with tumorigenesis and metastasis
Summary
At least one-third of epithelial ovarian cancers are associated with the development of ascites containing heterogeneous cell populations, including tumor cells, inflammatory cells, and stromal elements. The components of ascites and their effects on the tumor cell microenvironment remain poorly understood. In Taiwan ovarian cancer is the tenth leading cause of female malignancy and the leading cause of death from gynecological the initiation and progression of ovarian cancer is essential for the development of effective treatments. Prior research has established that ascites commonly develops in patients with EOC, and that the presence of abnormal stromal cells in the ascites may establish an unusual microenvironment for tumor spreading. The roles of these abnormal stromal cells in the development of ovarian cancer remain poorly understood
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