Abstract 719: ICAM3 and CCL16, inflammation genes screened by high-throughput siRNA library, govern cancer stemness in malignant tumors

Abstract

Abstract Cancer stem cells (CSCs) have the ability of both self-renewal and differentiation, were thought to be the main root of tumorigenesis, metastasis, recurrence and drug resistance. Current studies have focused on the maintenance of cancer stem cell abilities. Moreover, existing studies have shown that tumor associated inflammation microenvironment (TIM) play a pivotal role in different stages of tumor development. The linkage between inflammation and tumor stemness has been established. However, the evidence of TIM function on maintaining and nourishing CSCs properties remains insufficient. Here, we performed a high throughput siRNA interference platform to systemically screen out the inflammatory genes that regulate tumor stemness via OCT4 promoter linked reporter system in HMLE-Snail cells. 10 candidates were screened out which knockdown could both down-regulate OCT4 expression and decrease ALDH+ subpopulation. Furthermore, we validated the function of genes ICAM3 and CCL16 and found that knockdown ICAM3 or CCL16 inhibit cell migration, sphere formation in 231, A549 and HepG2 cell lines. We also found ICAM3 or CCL16 deficiency decrease side population and reduce chemo-resistance. In addition, mice bearing ICAM3 or CCL16 knockdown breast cancer cells develop smaller tumors and less lung metastases verse controls. Taken together, our study demonstrated that the inflammation related genes ICAM3 and CCL16 govern cancer cell migration and stemness in malignant tumors in vitro and in vivo, and that will provide new possible targets to CSCs for cancer therapy. Citation Format: Wenzhi Shen, Junling Xie, Renle Du, Shan Jiang, Xiaohe Luo, Huiwen He, Rong Xiang, Yunping Luo. ICAM3 and CCL16, inflammation genes screened by high-throughput siRNA library, govern cancer stemness in malignant tumors. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 719.