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

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...

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Published in:	BMC cancer Vol. 18; no. 1; p. 728
Main Authors:	Nushtaeva, Anna A, Stepanov, Grigory A, Semenov, Dmitry V, Juravlev, Evgeny S, Balahonova, Evgenia A, Gerasimov, Alexey V, Sidorov, Sergey V, Savelyev, Eugeniy I, Kuligina, Elena V, Richter, Vladimir A, Koval, Olga A
Format:	Journal Article
Language:	English
Published:	England BioMed Central Ltd 09-07-2018 BioMed Central BMC
Subjects:	Adjuvants, Immunologic - therapeutic use Analysis Apoptosis Breast cancer Breast Neoplasms - chemistry Breast Neoplasms - drug therapy Breast Neoplasms - pathology Cancer Cancer immunotherapy Cancer stem cells Cancer therapies Care and treatment CD24 Antigen - analysis CD44 Cell Line, Tumor Chemotherapy Endometrial cancer Epidermal growth factor Female Health aspects Hormone receptor Hormone receptors Humans Hyaluronan Receptors - analysis Immune system Immunoglobulins Immunostimulation Innate immunity Interferon Intracellular Signaling Peptides and Proteins - genetics Kidney cancer Messenger RNA Patient outcomes Primary culture Prognosis Prognostic marker Proteins Receptors, Estrogen - analysis Renal cell carcinoma RNA, Messenger - analysis Stem cells Tumors United States > US Hormone receptor Interferon-α Primary culture Breast cancer CD24 Cancer stem cells CD44 IFIT3 Prognostic marker snoRNA
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Summary:	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. 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. We revealed that BC5 carcinoma cells were PGR /ERb /ERa /Cyp19 , the BrCCh1 cells that originated from the recurrent tumour were PGR /ERb /ERa /Cyp19 , and normal BN cells were PGR /ERb /ERa /Cyp19 . 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. 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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1471-2407 1471-2407
DOI:	10.1186/s12885-018-4635-8