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BMC Cancer
Published in: BMC Cancer 1/2018

Open Access 01-12-2018 | Research article

Characterization of primary normal and malignant breast cancer cell and their response to chemotherapy and immunostimulatory agents

Authors: Anna A. Nushtaeva, Grigory A. Stepanov, Dmitry V. Semenov, Evgeny S. Juravlev, Evgenia A. Balahonova, Alexey V. Gerasimov, Sergey V. Sidorov, Eugeniy I. Savelyev, Elena V. Kuligina, Vladimir A. Richter, Olga A. Koval

Published in: BMC Cancer | Issue 1/2018

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Abstract

Background

The phenomenon of chemotherapy-resistant cancers has necessitated the development of new therapeutics as well as the identification of specific prognostic markers to predict the response to novel drugs. Primary cancer cells provide a model to study the multiplicity of tumourigenic transformation, to investigate alterations of the cellular response to various molecular stimuli, and to test therapeutics for cancer treatment.

Methods

Here, we developed primary cultures of human breast tissue – normal cells (BN1), cancer cells (BC5), and cells from a chemotherapy-treated tumour (BrCCh1) to compare their response to conventional chemotherapeutics and to innate immunity stimulators with that of the immortalized breast cells MCF7, MDA-MB-231, and MCF10A. Expression of the progesterone receptor (PGR), oestrogen receptor (ER) α and β, human epidermal growth factor receptor (HER) 2 and 3 and aromatase CYP19, as well as expression of interferon-induced protein with tetratricopeptide repeats 3 (IFIT3) mRNA in human breast cells were characterized.

Results

We revealed that BC5 carcinoma cells were PGRlow/ERbhigh/ERa−/Cyp19+, the BrCCh1 cells that originated from the recurrent tumour were PGR−/ERb+/ERa−/Cyp19+, and normal BN cells were PGR−/ERb+/ERa−/Cyp19high. The treatment of primary culture cells with antitumour therapeutics revealed that BrCCh1 cells were doxorubicine-resistant and sensitive to cisplatin. BC5 cells exhibited low sensitivity to tamoxifen and cisplatin. The innate immunity activators interferon-α and an artificial small nucleolar RNA analogue increased expression of IFIT3 at different levels in primary cells and in the immortalized breast cells MCF7, MDA-MB-231, and MCF10A. The relative level of activation of IFIT3 expression was inversely correlated with the baseline level of IFIT3 mRNA expression in breast cell lines.

Conclusion

Our data demonstrated that primary cancer cells are a useful model for the development of novel cancer treatments. Our findings suggest that expression of IFIT3 mRNA can be used as a prognostic marker of breast cancer cell sensitivity to immunostimulating therapeutics.
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Metadata
Title
Characterization of primary normal and malignant breast cancer cell and their response to chemotherapy and immunostimulatory agents
Authors
Anna A. Nushtaeva
Grigory A. Stepanov
Dmitry V. Semenov
Evgeny S. Juravlev
Evgenia A. Balahonova
Alexey V. Gerasimov
Sergey V. Sidorov
Eugeniy I. Savelyev
Elena V. Kuligina
Vladimir A. Richter
Olga A. Koval
Publication date
01-12-2018
Publisher
BioMed Central
Published in
BMC Cancer / Issue 1/2018
Electronic ISSN: 1471-2407
DOI
https://doi.org/10.1186/s12885-018-4635-8

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