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蛋白C受体是一组不同乳腺癌中的治疗干细胞靶点

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发表时间:2019-05-23 09:13作者:武汉新启迪Xinqidi来源:www.qidibio.com

蛋白C受体是一组不同乳腺癌中的治疗干细胞靶点


摘要

乳腺癌是一种异质性疾病。特别是,三阴性乳腺癌(TNBC)包括各种身份不明的分子亚组,目前几乎没有靶向治疗选择。我们之前的研究发现蛋白质C受体生殖)作为位于正常乳腺基底层的乳腺干细胞(MaSCs)的表面标记。鉴于TNBC与基层干细胞的可能联系,我们对生殖小鼠和人类乳腺癌。在小鼠乳腺肿瘤中,我们发现生殖细胞+细胞富含肿瘤干细胞Wnt1基底样肿瘤,但不在Brca1基底样肿瘤或PyVT内腔肿瘤。在人类癌症中,PROCR在一半的TNBC病例中得到强有力的表达。用病人来源的异种移植物(PDXs)进行的实验表明,PROR标记了这个离散亚组(称为PROR)中的干细胞+TNBC)。用抑制性纳米体干扰生殖细胞的功能可减少肿瘤干细胞数量,抑制肿瘤生长,防止肿瘤快速复发。我们的数据表明MaSC在乳腺肿瘤发生中起着关键作用。此外,我们的工作表明,生殖细胞可用作生物标志物,将TNBC分为临床相关亚组,并可能为这一临床重要肿瘤亚型提供新的靶向治疗策略。

参考文献

  1. 1.

    Foulkes, W. D., Smith, I. E. & Reis-Filho, J. S. Triple-negative breast cancer. N. Engl. J. Med. 363, 1938–1948 (2010).


  2. 2.

    Lehmann, B. D. et al. Identification of human triple-negative breast cancer subtypes and preclinical models for selection of targeted therapies. J. Clin. Invest. 121, 2750–2767 (2011).


  3. 3.

    Metzger-Filho, O. et al. Dissecting the heterogeneity of triple-negative breast cancer. J. Clin. Oncol. 30, 1879–1887 (2012).


  4. 4.

    Carey, L., Winer, E., Viale, G., Cameron, D. & Gianni, L. Triple-negative breast cancer: disease entity or title of convenience? Nat. Rev. Clin. Oncol. 7, 683–692 (2010).


  5. 5.

    Perou, C. M. et al. Molecular portraits of human breast tumours. Nature 406, 747–752 (2000).


  6. 6.

    Prat, A. et al. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res. 12, R68 (2010).


  7. 7.

    Adamo, B. & Anders, C. K. Stratifying triple-negative breast cancer: which definition(s) to use? Breast Cancer Res. 13, 105 (2011).


  8. 8.

    Visvader, J. E. & Lindeman, G. J. Cancer stem cells: current status and evolving complexities. Cell Stem Cell 10, 717–728 (2012).


  9. 9.

    Magee, J. A., Piskounova, E. & Morrison, S. J. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell 21, 283–296 (2012).


  10. 10.

    Nguyen, L. V., Vanner, R., Dirks, P. & Eaves, C. J. Cancer stem cells: an evolving concept. Nat. Rev. Cancer 12, 133–143 (2012).


  11. 11.

    Al-Hajj, M., Wicha, M. S., Benito-Hernandez, A., Morrison, S. J. & Clarke, M. F. Prospective identification of tumorigenic breast cancer cells. Proc. Natl Acad. Sci. USA 100, 3983–3988 (2003).


  12. 12.

    Ginestier, C. et al. ALDH1 is a marker of normal and malignant human mammary stem cells and a predictor of poor clinical outcome. Cell Stem Cell 1, 555–567 (2007).


  13. 13.

    Meyer, M. J. et al. CD44posCD49fhiCD133/2hi defines xenograft-initiating cells in estrogen receptor-negative breast cancer. Cancer Res. 70, 4624–4633 (2010).


  14. 14.

    Wang, D. et al. Identification of multipotent mammary stem cells by protein C receptor expression. Nature 517, 81–84 (2015).


  15. 15.

    Li, Y. et al. Evidence that transgenes encoding components of the Wnt signaling pathway preferentially induce mammary cancers from progenitor cells. Proc. Natl Acad. Sci. USA 100, 15853–15858 (2003).





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