Ovarian tumor initiating cell populations persist following paclitaxel and carboplatin chemotherapy treatment in vivo

• Paclitaxel and carboplatin treatment impedes tumor growth of a genetically defined mouse ovarian cancer cell line in vivo.
• Paclitaxel and carboplatin withdrawal results in tumor resurgence.
• Sca-1 and CD133 expressing cells persist post-Paclitaxel and carboplatin treatment.
• Sca-1+ and CD133+ cells form tumors rapidly, maintain tumor heterogeneity and express stem-cell related genes.
• Sca-1+ and CD133+ expressing cells represent populations of tumor initiating cells.

Development of recurrent platinum resistant disease following chemotherapy presents a challenge in managing ovarian cancer. Using tumors derived from genetically defined mouse ovarian cancer cells, we investigated the stem cell properties of residual cells post-chemotherapy. Utilizing CD133 and Sca-1 as markers of candidate tumor initiating cells (TIC), we determined that the relative levels of CD133+ and Sca-1+ cells were unaltered following chemotherapy. CD133+ and Sca-1+ cells exhibited increased stem cell-related gene expression, were enriched in G0/G1-early S phase and exhibited increased tumor initiating capacity, giving rise to heterogeneous tumors. Our findings suggest that residual TICs may contribute to recurrent disease.