Abstract
Abstract The tumor microenvironment plays a critical role in regulating breast cancer progression. Adipocytes differentiate from preadipocytes, which possess mesenchymal stem cell properties. Preadipocytes and adipocytes are essential components of the tumor microenvironment, and signaling between preadipocytes and breast cancer cells has been found to promote breast tumor formation and metastasis. Exosomes secreted from preadipocytes are also important components of the cancer stem cell niche. The primary goal of our studies is to examine how preadipocyte-derived exosomes can regulate early-stage breast cancer formation via regulating stem cell renewal. We use human and mouse preadipocytes and early-stage breast cancer cells (ductal carcinoma in situ, DCIS), as well as xenografts in immunodeficient mice to determine the role of preadipocyte secreted exosomes in DCIS stem cell behavior and tumor formation. By using protein arrays, we reveal CD81 and FLOT-1 as key exosomal protein markers and SOX2 and SOX9 as exosomal secretion of stem cell renewal regulators. We identify a key miR-140/SOX2/SOX9 axis that regulates differentiation, stemness, and migration in the tumor microenvironment. Next, we find that the natural antitumor compound shikonin can suppress preadipocyte signaling, inhibiting nearby DCIS cells. Through co-culture experiments we show that shikonin treated preadipocytes secrete exosomes containing high levels of miR-140 that can impact nearby DCIS cells through targeting SOX9 signaling. We demonstrate that preadipocyte-derived exosomes promote tumorigenesis in vivo, providing strong support for the importance of exosomal signaling in the tumor microenvironment. Finally, our data also show that targeting the tumor microenvironment may assist in blocking tumor formation. Citation Format: Benjamin Wolfson, Ramkishore Gernapudi, Nadire Duru, Qun Zhou. Preadipocyte exosomes promote early stage breast cancer formation by enhancing cancer stem cell renewal signaling. [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 5067. doi:10.1158/1538-7445.AM2015-5067
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
