Abstract
Abstract Prostate cancer (PCa) is promoted by white adipose tissue (WAT) overgrown in obesity. As an underlying mechanism, we have discovered the recruitment of adipose stromal cells (ASC) by tumors. We reported that CXCL1 expressed by cancer cells chemoattracts ASC expressing its receptor CXCR1. As a candidate upstream mechanism, we identified interleukin 22 secreted by WAT-infiltrating leukocytes and signaling through IL-22R in cancer cells. Our experiments in Hi-Myc mice indicate that obesity promotes epithelial-mesenchymal transition (EMT). We show that ASC directly induce EMT in adenocarcinoma cells. To test whether cancer progression can be blocked by ASC targeting, we have used a hunter-killer peptide D-WAT composed of an ASC-homing and a pro-apoptotic domain. D-WAT administration depleted prostate stromal cells expressing a chemokine SDF1α and suppressed the EMT. Our results indicate that ASC promote the EMT, at least in part, via SDF1a paracrine signaling and validate ASC as a therapeutic target. Citation Format: Mikhail Kolonin. Adipose stromal cells: A player in cancer progression and a therapeutic target [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr SY07-02. doi:10.1158/1538-7445.AM2017-SY07-02
Published Version
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