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

• Published in: BMC cancer 2018-07, Vol.18 (1), p.728-728, Article 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: Article
• Language: English
• 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
• ISSN: 1471-2407; 1471-2407
• DOI: 10.1186/s12885-018-4635-8

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.