Abstract

CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations. Screening revealed that, ovarian OVCAR-3, -4 and -5 and colon cancer HT-29, HCT-116 and SW620 over expressed both proteins. We aimed to isolate cells with stem cell features sorting the cells expressing CXCR4+CD133+ within ovarian cancer cell lines. The sorted population CD133+CXCR4+ demonstrated the highest efficiency in sphere formation in OVCAR-3, OVCAR-4 and OVCAR-5 cells. Moreover OCT4, SOX2, KLF4 and NANOG were highly expressed in CD133+CXCR4+ sorted OVCAR-5 cells. Most strikingly CXCR4+CD133+ sorted OVCAR-5 and -4 cells formed the highest number of tumors when inoculated in nude mice compared to CD133−CXCR4−, CD133+CXCR4−, CD133−CXCR4+ cells. CXCR4+CD133+ OVCAR-5 cells were resistant to cisplatin, overexpressed the ABCG2 surface drug transporter and migrated toward the CXCR4 ligand, CXCL12. Moreover, when human ovarian cancer cells were isolated from 37 primary ovarian cancer, an extremely variable level of CXCR4 and CD133 expression was detected. Thus, in human ovarian cancer cells CXCR4 and CD133 expression identified a discrete population with stem cell properties that regulated tumor development and chemo resistance. This cell population represents a potential therapeutic target.

Highlights

  • CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations

  • CD133 was clearly detectable in OVCAR-3, OVCAR-4 and OVCAR-5, ovarian cell lines and in KM-12, Colo-205, HT-29, HCT-116 and SW620 colon cancer cell lines

  • In addition higher mRNA for CD133 and CXCR4 was detected in 6/37 primary ovarian tissues compared to surrounding unaffected tissues (Fig. 4B). In this manuscript we took advantage of the NCI 60 cell lines to investigate the level of two putative cancer stem cell markers, CXCR4 and CD133

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Summary

Introduction

CD133 and CXCR4 were evaluated in the NCI-60 cell lines to identify cancer stem cell rich populations. In human ovarian cancer cells CXCR4 and CD133 expression identified a discrete population with stem cell properties that regulated tumor development and chemo resistance. This cell population represents a potential therapeutic target. With the intent to target cell populations with innate drug resistance and potential metastatic activity, the concomitant expression of CXCR4 and CD133 was evaluated in the NCI 60 tumor cell line panel comprising cell lines derived from hematopoietic malignancies and several solid tumors (lung cancer, central nervous system (CNS), colon, breast, ovarian, and prostate cancer and melanoma) extensively characterized for patterns of gene expression[6,7]. The aim of the study was to evaluate two putative cancer stem cell markers, CD133 and CXCR4, in the NCI 60 cell lines to identify a cancer stem cell rich population as in vitro models and suggestive for translational studies in patients

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