The stem cell markers Oct4A, Nanog and c-Myc are expressed in ascites cells and tumor tissue of ovarian cancer patients.
OBJECTIVE
The aim of this study was to examine the expression of established stem cell markers in ascites and tumor tissue obtained from ovarian cancer patients.


METHODS
Mononuclear cells present in ascites were collected by density gradient centrifugation. Intracellular flowcytometry was used to assess the putative presence of stem cell markers. RT-PCR was used to detect full length Oct4A, a splice variant Oct4B, implicated in glioma and breast cancer, Oct4 pseudogenes and c-Myc. Genes were cloned and sequenced to determine putative mutations. Confocal laser scanning microscopy was performed to localize the markers in ascites cells as well as in tumor tissue. Material from carcinomas other than epithelial ovarian carcinoma served as control.


RESULTS
A small quantity of cells in ascites and in tumor tissue of ovarian cancer patients was detected that expresses c-Myc, Oct4A and Nanog. Besides Oct4A, present in the nucleus, also the cytoplasmic resident Oct4B splice variant was detected. Remarkably, c-Myc was found partially in the cytoplasm. Since no mutations in c-Myc were found that could explain the cytoplasmic localization, we hypothesize that this is due an IL-6 induced c-Myc shuttle factor.


CONCLUSIONS
The expression of stem cell genes was detected in a small proportion of tumor cells present in ascites as well as in tumor tissue. IL-6 plays an important role in the induction of c-Myc.
Department of Tumor Immunology, Nijmegen Centre for Molecular Life Sciences, Radboud University Nijmegen Medical Centre, PO Box 9101, 6500HB, Nijmegen, The Netherlands.
Jiabo
J
Di
Tjitske
T
Duiveman-de Boer
Petra L M
PL
Zusterzeel
Carl G
CG
Figdor
Leon F A G
LF
Massuger
Ruurd
R
Torensma
D001201:Ascites / Q000378:metabolism*; D005260:Female; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000378:metabolism*; D010051:Ovarian Neoplasms / Q000378:metabolism*; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*
D018398:Homeodomain Proteins; C489427:MYC protein, human; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; D016271:Proto-Oncogene Proteins c-myc