CCR: human endometrial CSC

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Clin Cancer Res. 2009 Jul 1;15(13):4299-311. Epub 2009 Jun 9. Related Articles, LinkOut 1 ?) v9 H2 S2 N/ i1 o6 i

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Cells with characteristics of cancer stem/progenitor cells express the CD133 antigen in human endometrial tumors.
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Rutella S, Bonanno G, Procoli A, Mariotti A, Corallo M, Prisco MG, Eramo A, Napoletano C, Gallo D, Perillo A, Nuti M, Pierelli L, Testa U, Scambia G, Ferrandina G.
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Department of Hematology and Department of Gynecology, Catholic University Medical School, USA. srutella@rm.unicatt.it- K3 {: D+ z6 R' d' Y
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PURPOSE: Cancer stem cells represent an attractive therapeutic target for tumor eradication. The present study aimed to determine whether CD133 expression may identify cells with characteristics of cancer stem/progenitor cells in human endometrial tumors. EXPERIMENTAL DESIGN: We analyzed 113 tumor samples for CD133/1 expression by flow cytometry, immunohistochemistry, and semiquantitative reverse transcription-PCR. CD133(+) cells were isolated and used to assess phenotypic characteristics, self-renewal capacity, ability to maintain CD133 expression and form sphere-like structures in long-term cultures, sensitivity to chemotherapeutic agents, gene expression profile, and ability to initiate tumors in NOD/SCID mice. RESULTS: Primary tumor samples exhibited a variable degree of immunoreactivity for CD133/1, ranging from 1.3% to 62.6%, but stained negatively for other endothelial and stem cell-associated markers. Isolated CD133(+) cells expanded up to 4.6-fold in serum-replenished cultures and coexpressed the GalNAcalpha1-O-Ser/Thr MUC-1 glycoform, a well-characterized tumor-associated antigen. Dissociated bulk tumors formed sphere-like structures; cells grown as tumor spheres maintained CD133 expression and could be propagated for up to 12 weeks. CD133(+) cells purified from endometrioid adenocarcinomas were resistant to cisplatin-induced and paclitaxel-induced cytotoxicity and expressed a peculiar gene signature consisting of high levels of matrix metalloproteases, interleukin-8, CD44, and CXCR4. When serially transplanted into NOD/SCID mice, CD133(+) cells were capable of initiating tumor formation and recapitulating the phenotype of the original tumor. CONCLUSIONS: CD133 is expressed by human endometrial cancers and might represent a valuable tool to identify cells with cancer stem cell characteristics.3 b% F; K* Y, v
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Publication Types: % `' T5 a; h5 j# U
Evaluation Studies1 c9 K4 `4 |; e& k  `/ i
Research Support, Non-U.S. Gov't2 _! c5 S4 Q# n) N& q4 I2 F$ w
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PMID: 19509143) D: X' Z" o7 \4 G' E
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