CD24+ Ovarian cancer cells are enriched for cancer-initiating cells and dependent on JAK2 signaling for growth and metastasis

Daniela Burgos-Ojeda, Rong Wu, Karen McLean, Yu Chih Chen, Moshe Talpaz, Euisik Yoon, Kathleen R. Cho, Ronald J. Buckanovich

Research output: Contribution to journalArticle

47 Citations (Scopus)

Abstract

Ovarian cancer is known to be composed of distinct populations of cancer cells, some of which demonstrate increased capacity for cancer initiation and/or metastasis. The study of human cancer cell populations is difficult due to long requirements for tumor growth, interpatient variability, and the need for tumor growth in immune-deficient mice. We therefore characterized the cancer initiation capacity of distinct cancer cell populations in a transgenic murine model of ovarian cancer. In this model, conditional deletion of Apc, Pten, and Trp53 in the ovarian surface epithelium (OSE) results in the generation of high-grade metastatic ovarian carcinomas. Cell lines derived from these murine tumors express numerous putative stem cell markers, including CD24, CD44, CD90, CD117, CD133, and ALDH. We show that CD24+ and CD133+ cells have increased tumor sphere-forming capacity. CD133+ cells demonstrated a trend for increased tumor initiation while CD24+ cells versus CD24- cells had significantly greater tumor initiation and tumor growth capacity. No preferential tumor-initiating or growth capacity was observed for CD44+, CD90+, CD117+, or ALDH+ versus their negative counterparts. We have found that CD24+ cells, compared with CD24- cells, have increased phosphorylation of STAT3 and increased expression of STAT3 target Nanog and c-myc. JAK2 inhibition of STAT3 phosphorylation preferentially induced cytotoxicity in CD24+ cells. In vivo JAK2 inhibitor therapy dramatically reduced tumor metastases, and prolonged overall survival. These findings indicate that CD24+ cells play a role in tumor migration and metastasis and support JAK2 as a therapeutic target in ovarian cancer.

Original languageEnglish
Pages (from-to)1717-1727
Number of pages11
JournalMolecular Cancer Therapeutics
Volume14
Issue number7
DOIs
Publication statusPublished - 2015 Jul 1

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'CD24<sup>+</sup> Ovarian cancer cells are enriched for cancer-initiating cells and dependent on JAK2 signaling for growth and metastasis'. Together they form a unique fingerprint.

  • Cite this