Tumor associated macrophages have been shown to play key roles in tumor progression in different cancer types including lung. Here we investigated the role of M2-tumor associated macrophages (TAMs) in the generation of lung cancer stem cells (LCSCs) and the potential of modulating TAMs to inhibit the generation of LCSCs. Elevated Muc1 expression has been reported in inflammatory lung macrophages and associated with lung cancer development. We first found that Muc1 is overexpressed in lung cancer patients and associated with poor survival rates from public database; importantly, we showed that when co-cultured with TAMs, the level of Muc1 along with stemness genes significantly increased in lung cancer cells. Pterostilbene dose-dependently suppressed self-renewal ability in TAMs-cocultured lung cancer cells via downregulating Muc1, NF-kB, CD133, β-catenin and Sox2 expression. Subsequently, we demonstrated Muc1-silenced TAMs exhibited a significantly lower ability to promote the generation of LCSCs and a decreased level of NF-kB, CD133 and Sox2. Collectively, we demonstrated that Muc1 played an important role in TAMs-induced LCSC generation and pterostilbene treatment inhibited this phenomenon. Modulation of TAMs using pterostilbene may be of future clinical use for treating lung cancer patients.

Note: This abstract was not presented at the meeting.

Citation Format: Wen-Chien Huang. Phytochemical pterostilbene suppresses lung cancer stem cell generation via modulating tumor-associated macrophages. [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 412. doi:10.1158/1538-7445.AM2015-412

©2015 American Association for Cancer Research.
2015