- 作者: Chih-Ming Ho, Shwu-Fen Chang, Chih-Chiang Hsiao, Tsai-Yen Chien and Daniel Tzu-Bi Shih
- 作者服務機構: Gynecologic Cancer Center, Department of Obstetrics and Gynecology, Cathay General Hospital, Taipei, Taiwan
- 中文摘要: --
- 英文摘要:
Background: 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. This
study aimed to isolate and characterize stromal progenitor cells from the ascites of
patients with epithelial ovarian adenocarcinoma (EOA).
Methods: Seventeen 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.
Results: The 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. Conclusion: The 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. - 中文關鍵字: --
- 英文關鍵字: human cancer initiating/stem cell; stromal progenitor cells; epithelial ovarian adenocarcinoma; epithelial-mesenchymal transition