WNT/β-catenin mediates radiation resistance of mouse mammary progenitor cells

Abstract

), the authors note that in Fig. 1D Right, the x-axis labels were transposed. The corrected figure and its legend appear below. MECs were isolated from BALB/c mice, cultured for 3 days, irradiated, and analyzed for %SP by Hoechst 33342 staining and flow cytometry. Radiation selectively increased the progenitor fraction (%SP) (P ϭ 0.015 for 2 Gy, 0.008 for 4 Gy, and 0.05 for 6 Gy by the two-tailed t test). (B) MCF-7 cells were analyzed for %SP by Hoechst 33342 staining and flow cytometry. Radiation selectively increased the progenitor fraction (%SP) (P ϭ 0.05 for 0 Gy vs. 4 Gy by the two-tailed t test). (C) Cells were analyzed for Sca1 in the SP 24 h after irradiation. Radiation selectively increased the Sca1 ϩ (progenitor) fraction within the SP by killing the more sensitive Sca1 Ϫ (nonprogenitor) cells (P Ͻ 0.05 for Sca1 ϩ to Sca1 Ϫ at 0 Gy vs. 2-8 Gy). The differences in effects of doses of 2 Gy vs. higher doses were not significant. (D) Anesthetized BALB/c mice were immobilized supine, and mammary glands (entire ventral surface) were irradiated. MECs were isolated 48 h after irradiation and analyzed immediately for Sca1 by flow cytometry. Radiation selectively increased the Sca1 ϩ (progenitor) fraction and decreased the Sca1 Ϫ (nonprogenitor)

Application of Stem Cells in Targeted Therapy of Breast Cancer: A Systematic Review

“…Nine out of 32 studies, with heterogeneous study design, met the predefined inclusion criteria and all were reviewed Of these, six studies were phase I (Dwyer et al, 2007;Woodward et al, 2007;Vlashi et al, 2009;Grisendi et al, 2010;Dwyer et al, 2011;Milane et al, 2011)and three were phase II clinical trials (Table 1) (Ueno et al, 2009;Resetkova et al, 2010;Viens et al, 2010). There was no published paper regarding phase III clinical trial on stem cell targeted therapy of breast cancer within the period of this study.…”

Cancer stem cells in glioblastoma—molecular signaling and therapeutic targeting

“…It seems that multiple molecular mechanisms regulate GSC radioresistance, perhaps with intertumoral variation. Interestingly, decreased radiosensitivity in breast cancer stem cells has been linked to lower levels reactive oxygen species (ROS) (Diehn et al, 2009) or enhanced activity of Wnt/β-catenin signaling (Woodward et al, 2007). Although these mechanisms have not been reported in GSCs, they give hope that several molecular regulators may be targeted synergistically in GSCs in order to effectively overcome radioresistance.…”

“…Wnt signaling is activated predominantly in medulloblastoma of the classic subtype (Thompson et al, 2006). Recent studies indicated that Wnt-β-catenin signaling may contribute to radioresistance in cancer stem cells (Woodward et al, 2007). Whether Wnt-β-catenin signaling is associated with GSC maintenance and radioresistance requires further investigation, but it is possible that Wnt blockade can effectively and specifically target cancer stem cells in glioblastomas.…”

The BMP2/7 heterodimer inhibits the human breast cancer stem cell subpopulation and bone metastases formation

“…CSCs appear more resistant to several conventional therapies than their non-CSC counterparts (Woodward et al, 2007;Li et al, 2008;Creighton et al, 2009), underscoring the need for developing CSC-directed therapies. Although breast CSCs may arise as the result of EMT (Mani et al, 2008;Hollier et al, 2009;Wellner et al, 2009;Kong et al, 2010;Singh and Settleman, 2010), the current findings support the notion that this intrinsic epithelial plasticity of cancer cells can also be exploited to inhibit their invasiveness and metastatic potential by using selected BMPs.…”