Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism

  • Authors:
    • Yanchen Liu
    • Tianbiao Zou
    • Shuhuai Wang
    • Hong Chen
    • Dongju Su
    • Xiaona Fu
    • Qingyuan Zhang
    • Xinmei Kang
  • View Affiliations

  • Published online on: January 19, 2016     https://doi.org/10.3892/ijo.2016.3351
  • Pages: 1063-1072
Metrics: Total Views: 0 (Spandidos Publications: | PMC Statistics: )
Total PDF Downloads: 0 (Spandidos Publications: | PMC Statistics: )


Abstract

It is believed that breast cancer stem cells (BCSCs), like normal stem cell counterparts, have the capacity of self-renewal and differentiation. Simultaneously, estrogen receptor (ER)-negative (-) BCSCs are affected by surrounding differentiated ER-positive (+) tumor cells by virtue of paracrine signaling within the tumor micro­environment. Genistein (GEN), as a sort of phytoestrogen, can act on ER+ breast cancer cells but the role of GEN in the differentiation of neighboring ER- BCSCs has not been defined. Transwell co-culture system was utilized so as to elaborate the interaction between well-differentiated ER+ breast cancer cells (MCF-7) and ER- breast cancer stem/progenitor cells (mammospheres derived from MDA-MB-231 cells). GEN-induced differentiation of BCSCs was analyzed by mammospheres formation assay, flow cytometry and RT-PCR after a 3 day solo-culture or co-culture. We find that GEN sized 2 µM, and 40 nM, effectively promotes morphological alteration of mammospheres, reduces the ratio of subset of CD44+/CD24-/ESA+ cells and upregulates the expression of differentiated cell markers of mammospheres in co-culture system, but not in solo-culture condition. Besides, we demonstrate that the differentiation-inducing effect of GEN on mammospheres is associated with PI3K/Akt and MEK/ERK signaling pathways which are activated by amphiregulin released from ER+ cancer cells. These results indicate that GEN was able to induce the differentiation of breast cancer stem/progenitor cells through interaction with ER+ cancer cells by a paracrine mechanism.
View Figures
View References

Related Articles

Journal Cover

March 2016
Volume 48 Issue 3

Print ISSN: 1019-6439
Online ISSN:1791-2423

Sign up for eToc alerts

Recommend to Library

Copy and paste a formatted citation
APA
Liu, Y., Zou, T., Wang, S., Chen, H., Su, D., Fu, X. ... Kang, X. (2016). Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism. International Journal of Oncology, 48, 1063-1072. https://doi.org/10.3892/ijo.2016.3351
MLA
Liu, Y., Zou, T., Wang, S., Chen, H., Su, D., Fu, X., Zhang, Q., Kang, X."Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism". International Journal of Oncology 48.3 (2016): 1063-1072.
Chicago
Liu, Y., Zou, T., Wang, S., Chen, H., Su, D., Fu, X., Zhang, Q., Kang, X."Genistein-induced differentiation of breast cancer stem/progenitor cells through a paracrine mechanism". International Journal of Oncology 48, no. 3 (2016): 1063-1072. https://doi.org/10.3892/ijo.2016.3351