Abstract LB-356: Maintenance of breast cancer stem-like cells by cancer associated fibroblast-derived soluble factors

Accumulating evidence indicates the presence of cancer stem cells (CSCs) or tumor initiating cells in many types of tumors, which would be the leading cause of poor prognosis of tumor patients. They are defined as cell populations which have self-renewal ability and multi-differentiation capacity, and have been thought to greatly contribute to tumor initiation, recurrence and metastasis. CSCs are also known to be highly resistant to conventional therapies. Therefore, developing CSC targeting therapy is in urgent need to eradicate cancer cells efficiently. Stem cell properties of CSCs are thought to be maintained by the interaction with the tumor microenvironment, suggesting that it is important to identify factors which mediate such an interaction between cancer cells and the microenvironment. In this study, we focused on cancer-associated fibroblasts (CAFs) that forms the great part of breast tumor microenvironment and investigated how CAFs influence the functions of CSCs. By sphere forming assay, we found that some soluble factors secreted by CAFs induced growth of CSC-like populations. Then, to identify which factors are upregulated when fibroblasts get CAF-like properties, we compared transcriptomes of fibroblasts which were cultured with or without clinical sample-derived breast cancer cells by RNA-seq analysis. We found two genes in the same gene family were highly upregulated in co-cultured cells and they could induce sphere forming ability of CSCs. We are advancing our research based on a hypothesis that these two factors contribute to maintenance of stem cell functions of CSCs. Here, we will introduce results obtained by recent experiments. Citation Format: Takahiko Murayama, Tatsunori Nishimura, Arinobu Tojo, Noriko Gotoh. Maintenance of breast cancer stem-like cells by cancer associated fibroblast-derived soluble factors [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-356.