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

Characterization of primary normal and malignant breast cancer cell and their response to chemotherapy and immunostimulatory agents.
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DOI:
10.1186/s12885-018-4635-8
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发表时间:
2018-07-09
期刊:
影响因子:
3.8
通讯作者:
Koval OA
Koval OA
中科院分区:
医学2区
文献类型:
--
作者:
Nushtaeva AA;Stepanov GA;Semenov DV;Juravlev ES;Balahonova EA;Gerasimov AV;Sidorov SV;Savelyev EI;Kuligina EV;Richter VA;Koval OA

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化疗耐药癌症的现象需要开发新的治疗方法以及鉴定特异性预后标志物以预测对新药的反应。原代癌细胞提供了一个模型来研究肿瘤发生转化的多样性,研究细胞对各种分子刺激的反应的改变,并测试癌症治疗的治疗方法。在这里,我们开发了人类乳腺组织-正常细胞(BN 1),癌细胞(BC 5)和化疗治疗肿瘤细胞(BrCCh 1)的原代培养物,以比较它们对常规化疗药物和先天免疫刺激剂的反应与永生化乳腺细胞MCF 7,MDA-MB-231和MCF 10 A的反应。对人乳腺细胞中孕激素受体(PGR)、雌激素受体(ER)α和β、人表皮生长因子受体(HER)2和3以及芳香酶CYP 19的表达以及干扰素诱导的三肽重复序列3(IFIT 3)mRNA的表达进行了表征。我们发现,BC 5癌细胞是PGR低/ERb高/ERa−/Cyp 19+,来自复发肿瘤的BrCCh 1细胞是PGR−/ERb+/ERa−/Cyp 19+,正常BN细胞是PGR−/ERb+/ERa−/Cyp 19高。原代培养细胞的抗肿瘤治疗显示,BrCCh 1细胞阿霉素耐药和顺铂敏感。BC 5细胞对三苯氧胺和顺铂的敏感性较低。先天免疫激活剂干扰素-α和人工小核仁RNA类似物在原代细胞和永生化乳腺细胞MCF 7、MDA-MB-231和MCF 10 A中以不同水平增加IFIT 3的表达。IFIT 3表达的相对活化水平与乳腺细胞系中IFIT 3 mRNA表达的基线水平呈负相关。我们的数据表明,原代癌细胞是开发新型癌症治疗的有用模型。我们的研究结果表明,IFIT 3 mRNA的表达可以作为乳腺癌细胞对免疫刺激疗法敏感性的预后标志物。
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 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. 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.
DOI: 10.1038/bjc.2015.398
发表时间: 2016-01-19
影响因子: 8.8
作者:
Legrier ME;Bièche I;Gaston J;Beurdeley A;Yvonnet V;Déas O;Thuleau A;Château-Joubert S;Servely JL;Vacher S;Lassalle M;Depil S;Tucker GC;Fontaine JJ;Poupon MF;Roman-Roman S;Judde JG;Decaudin D;Cairo S;Marangoni E
通讯作者: Marangoni E
DOI: 10.1126/sciadv.1501924
发表时间: 2016-06
期刊: Science advances
影响因子: 13.6
作者:
Singhal H;Greene ME;Tarulli G;Zarnke AL;Bourgo RJ;Laine M;Chang YF;Ma S;Dembo AG;Raj GV;Hickey TE;Tilley WD;Greene GL
通讯作者: Greene GL
DOI: 10.1186/bcr3329
发表时间: 2012-10-12
期刊: Breast cancer research : BCR
影响因子: --
作者:
Aceto N;Duss S;MacDonald G;Meyer DS;Roloff TC;Hynes NE;Bentires-Alj M
通讯作者: Bentires-Alj M
DOI: 10.1007/978-3-319-42044-8_24
发表时间: 2016-01-01
期刊: CIRCULATING NUCLEIC ACIDS IN SERUM AND PLASMA - CNAPS IX
影响因子: --
作者:
Stepanov, Grigory A.;Filippova, Julia A.;Semenov, Dmitriy V.
通讯作者: Semenov, Dmitriy V.
DOI: 10.1186/gb-2014-15-3-r47
发表时间: 2014-03-03
期刊: Genome biology
影响因子: 12.3
作者:
Geeleher P;Cox NJ;Huang RS
通讯作者: Huang RS