| First Author | Burgos-Ojeda D | Year | 2015 |
| Journal | Mol Cancer Ther | Volume | 14 |
| Issue | 7 | Pages | 1717-27 |
| PubMed ID | 25969154 | Mgi Jnum | J:317265 |
| Mgi Id | MGI:6851795 | Doi | 10.1158/1535-7163.MCT-14-0607 |
| Citation | Burgos-Ojeda D, et al. (2015) CD24+ Ovarian Cancer Cells Are Enriched for Cancer-Initiating Cells and Dependent on JAK2 Signaling for Growth and Metastasis. Mol Cancer Ther 14(7):1717-27 |
| abstractText | 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. |
