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CD44+/CD24− ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival

Abstract

Cancer cells with the surface marker profile CD44+/CD24− have previously been described to possess cancer stem cell-like properties. This manuscript evaluates those properties in ovarian cancer cell lines. The proportion of CD44+/CD24− cells corresponded to the clinical aggressiveness of each ovarian cancer cell line histologic subtype. CD44+/CD24− cells demonstrated enhanced progressive differentiation as well as showing a 60-fold increase in Matrigel invasion in both SKOV3 and OV90 cell lines (p < 0.001 each) compared to other phenotypes. CD44+/CD24− demonstrated significant resistance to all chemotherapy agents used in all cell lines, with a 71–93 % increase in resistance compared with baseline. Using a threshold of 25 % CD44+/CD24– ovarian cancer cells found in ascites, patients with >25 % CD44+/CD24− were significantly more likely to recur (83 vs. 14 %, p = 0.003) and had shorter median progression-free survival (6 vs. 18 months, p = 0.01). In conclusion, the CD44+/CD24− phenotype in ovarian cancer cells demonstrate cancer stem cell-like properties of enhanced differentiation, invasion, and resistance to chemotherapy. This CD44+/CD24− phenotype correlates to clinical endpoints with increased risk of recurrence and shorter progression-free survival in patients with ovarian cancer.

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Abbreviations

bFGF:

Basic fibroblast growth factor

BSA:

Bovine serum albumin

CK7:

Cytokeratin 7

EGF:

Epidermal growth factor

FACS:

Fluorescence-activated cell sorting

FCM:

Flow cytometry

FITC:

Fluorescein isothiocyanate

PFS:

Progression free survival

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Acknowledgments

This work was supported by the Gynecologic Cancer Foundation Ovarian Cancer Research Award: Sherri’s From a Whisper to a Roar, Women’s Motorcycle Foundation Award.

Conflict of interest

The authors declare that they have no conflict of interests to disclose.

Author information

Correspondence to Rodney P. Rocconi.

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Meng, E., Long, B., Sullivan, P. et al. CD44+/CD24− ovarian cancer cells demonstrate cancer stem cell properties and correlate to survival. Clin Exp Metastasis 29, 939–948 (2012). https://doi.org/10.1007/s10585-012-9482-4

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Keywords

  • CD44+/CD24−
  • Ovarian cancer
  • Cancer stem-like cells
  • Chemoresistance
  • Survival