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- W2015617538 abstract "Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DCRecent evidence suggests that the molecular heterogeneity inherent to breast cancer, which underlies metastasis, resistance to treatment and disease recurrence, can be driven by a distinct subpopulation of tumor cells referred to as cancer stem cells (CSCs). However, the extracellular cues and intracellular pathways that CSCs rely on remain unclear. Working with a breast cancer progression model system we found the invasive breast cancer cell line to exhibit numerous stem-like characteristics. Gene expression profiling, along with a careful review of the literature, identified a secreted extracellular matrix molecule, periostin (POSTN), which we hypothesized to be required for the maintenance of a cancer stem cell state. POSTN expression was increased in numerous basal-like breast cancer cell lines that contain an expanded CSC population, as well as in cells grown as mammospheres and in the CD44+/CD24- fraction of tumor cells. Furthermore, CSC-like lines displayed increased surface levels of the alpha-v beta-3 integrin heterodimer, a known receptor for POSTN, suggesting that hyperactivation of a POSTN signaling axis could potentially regulate the CSC state. Using stable cell lines expressing an shRNA directed at POSTN we have found that POSTN is required for efficient mammosphere formation and for the maintenance of an ALDH-positive CSC population. In line with this, we found these cells had impaired Erk and Wnt signaling and expressed less IL-6 and IL-8, known regulators of CSCs. Furthermore, high POSTN expression correlates with a worse clinical prognosis in basal-like breast cancer patients. Therefore, we suggest that POSTN signaling through integrin receptors may enrich for highly tumorigenic breast CSCs in a subset of basal-like tumors, leading to aggressive and recurrent malignancies. More broadly, our results imply that a supportive tumor niche can be established and maintained by cancer cells, and raises the possibility of targeting components of this extracellular environment to eradicate breast CSCs.Citation Format: Arthur W. Lambert, Sait Ozturk, Panos Papageorgis, Hamid Abdolmaleky, Sam Thiagalingam. Periostin signaling regulates breast cancer stem cells. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 4890. doi:10.1158/1538-7445.AM2013-4890" @default.
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- W2015617538 date "2013-04-15" @default.
- W2015617538 modified "2023-09-25" @default.
- W2015617538 title "Abstract 4890: Periostin signaling regulates breast cancer stem cells." @default.
- W2015617538 doi "https://doi.org/10.1158/1538-7445.am2013-4890" @default.
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