Abstract 5062: Ovarian cancer cells induce the microenvironment changes and subsequently promote disease propagation and dissemination through epithelial-mesenchymal transition and enrichment of tumorigenic cells

Ovarian cancer has the highest mortality rate of all gynecological cancers primarily due to the high incidence of metastatic spread prior to diagnosis. Understanding the biology of this malignancy and developing models that reflect the patient disease phenotype will create opportunities for testing targeted therapy. We used the Ovcar 3 cell line to establish a metastasis model through serial in vivo passage. After the treatment of docetaxel and carboplatin, the characteristics of minimal residual disease were assessed. Notably, the stromal environment and tumor initiating subpopulation play critical roles on the Ovcar 3 MET disease invasiveness and progression. Compared to the molecular profile of the parental cells, these invasive Ovcar 3 MET cells exhibited higher expressions of β-catenin, slug, N-cadherin and ZEB1, suggesting the epithelial-mesenchymal transition in these Ovcar 3 MET cells. In addition, a higher fraction of the CD44+/CD24- subpopulation was found in the Ovcar 3 MET cells, suggesting enrichment of the tumorigenic population. With the treatment of chemotherapeutic agents, we observed an enrichment of CD44+/CD24- subpopulation in the minimal residual disease. The self-renewal functional analysis demonstrated a higher tumorigenic potential of the MRD cells compared to the cells from vehicle treated mice. In contrast, treatment of the dual PI3K/mTOR inhibitor PF-04691502 resulted in significant anti-tumor and anti-metastatic activities without increasing the MRD self-renewal potential. These results warrant the combination assessment of chemotherapy with targeted agents to reduce or eradicate MRD, therefore to mitigate the risk of disease relapse. Citation Format: Nanni Huser, Zhengming Yan, Jing Yuan, Cathy C. Zhang. Ovarian cancer cells induce the microenvironment changes and subsequently promote disease propagation and dissemination through epithelial-mesenchymal transition and enrichment of tumorigenic cells. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 5062. doi:10.1158/1538-7445.AM2015-5062