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WNT, Hedgehog and NOTCH signaling pathways in triple negative breast cancer with high and low content of cancer stem cells

Date

03 May 2019

Session

Poster lunch

Presenters

Aleksandr Brilliant

Citation

Annals of Oncology (2019) 30 (suppl_3): iii1-iii26. 10.1093/annonc/mdz095

Authors

A. Brilliant1, Y. Brilliant2, S. Sazonov3

Author affiliations

  • 1 Department Of Pathomorthology, Institute of Medical Cell Technologies, 620137 - Ekaterinburg/RU
  • 2 Department Of Pathomorthology, Institute of Medical Cell Technologies, Ekaterinburg/RU
  • 3 Histology, Cytology And Embryology, Ural State Medical University, 620028 - Ekaterinburg/RU
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Background

Triple negative breast cancer is at the greatest interest for the study. Cells of this type of breast cancer do not have receptors for steroid hormones or tyrosine kinases. For successful treatment of triple negative cases additional points of application are needed. Such targets could be cancer stem cells. For these types of cells, as well as for other stem cells, there are three main cascades are typical - WNT, Hedgehog and NOTCH. However, the conducted studies indicate the existence of other signaling mechanisms of regulation. In our work, we investigated the expression of the NF-kB, PI3K signaling pathways, as well as WNT, Hedgehog, NOTCH in cells of triple negative breast cancer with high and low content of cancer stem cells (ALDH1A1 level).

Methods

The material of 54 cases of infiltrative breast cancer was used. To determine the presence of stem cells in tumor population, the presence of ALDH1A1 protein in cancer cells was investigated. Expression of steroid hormone receptors, HER-2 and Ki-67 was studied by immunohistochemical method to identify cases of triple negative breast cancer. The expression of signaling molecules PI3K, NF-kB, WNT, Notch, Hedgehog was also explored by innunohistochemical method.

Results

All cases were investigated for ALDH1A1 expression and were divided into two groups - with low (expression of ALDH1A1 was estimated as 0 and 1+) and high (expression of ALDH1A1 was estimated as 2+ and 3+) content of cancer stem cells. It was found that 20% of cases of triple negative breast cancer are positive for ALDH1A1. Expression of explored signaling molecules in cases with high and low content of cancer stem cells is shown in the table.

Table: 40P

NF-kBPI3KPTENNOTCHWNTHH
high ALDH1A1100%100%33%11%11%0%
low ALDH1A1100%100%20%25%33%14%

Conclusions

It was found that cases with high content of cancer stem cells are less regulated by signaling pathways NOTCH and WNT. Expression of NF-Kb and PI3K signaling molecules (which are responsible for activation of eponymous signaling pathways) appeared in all studied cases, while expression of PTEN phosphatase, which inhibits PI3K signaling pathway, was more common for cases with high content of cancer stem cells.

Editorial acknowledgement

Clinical trial identification

Legal entity responsible for the study

Institute of Medical Cell Technologies, Ekaterinburg, Russian Federation.

Funding

Ministry of Healthcare of Sverdlovsk Region of Russian Federation.

Disclosure

All authors have declared no conflicts of interest.

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