TY - JOUR

T1 - Characterization of primary normal and malignant breast cancer cell and their response to chemotherapy and immunostimulatory agents

AU - Nushtaeva, Anna A.

AU - Stepanov, Grigory A.

AU - Semenov, Dmitry V.

AU - Juravlev, Evgeny S.

AU - Balahonova, Evgenia A.

AU - Gerasimov, Alexey V.

AU - Sidorov, Sergey V.

AU - Savelyev, Eugeniy I.

AU - Kuligina, Elena V.

AU - Richter, Vladimir A.

AU - Koval, Olga A.

N1 - Publisher Copyright: © 2018 The Author(s).

PY - 2018/7/9

Y1 - 2018/7/9

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Cancer stem cells

KW - CD24

KW - CD44

KW - Hormone receptor

KW - IFIT3

KW - Interferon-α

KW - Primary culture

KW - Prognostic marker

KW - SnoRNA

KW - Hyaluronan Receptors/analysis

KW - CD24 Antigen/analysis

KW - Humans

KW - Receptors, Estrogen/analysis

KW - Adjuvants, Immunologic/therapeutic use

KW - Intracellular Signaling Peptides and Proteins/genetics

KW - Cell Line, Tumor

KW - Female

KW - RNA, Messenger/analysis

KW - Breast Neoplasms/chemistry

KW - MOLECULAR SUBTYPES

KW - ACTIVATION

KW - SENSITIVITY

KW - HEPATOCELLULAR-CARCINOMA

KW - Interferon-alpha

KW - ADENOCARCINOMA

KW - QUANTIFICATION

KW - PHENOTYPE

KW - snoRNA

KW - EPITHELIAL-MESENCHYMAL TRANSITION

KW - STEM-CELL

KW - PERSONALIZED-MEDICINE

UR - http://www.scopus.com/inward/record.url?scp=85049793867&partnerID=8YFLogxK

U2 - 10.1186/s12885-018-4635-8

DO - 10.1186/s12885-018-4635-8

M3 - Article

C2 - 29986702

AN - SCOPUS:85049793867

VL - 18

SP - 728

JO - BMC Cancer

JF - BMC Cancer

SN - 1471-2407

IS - 1

M1 - 728

ER -