brca1突变的乳腺癌细胞系与脂肪源性基质细胞(ADSCs)的相互作用

IF 3 4区 医学 Q2 ENDOCRINOLOGY & METABOLISM Journal of Mammary Gland Biology and Neoplasia Pub Date : 2021-09-01 Epub Date: 2021-07-06 DOI:10.1007/s10911-021-09493-4
Adelina Plangger, Werner Haslik, Barbara Rath, Christoph Neumayer, Gerhard Hamilton
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引用次数: 1

摘要

对于BRCA1或BRCA2基因突变的患者,脂质填充可能是预防性乳房切除术后辅助乳房重建的一种技术。然而,迄今为止,尚不清楚脂肪源性基质细胞(ADSCs)是否会增加这种情况下肿瘤发生和进展的风险。因此,本研究探讨了BRCA1突变的乳腺癌细胞系与正常ADSCs的相互作用。比较MDA-MB-436 (BRCA1 c.5277 + 1G > A)和HCC1937 (BRCA1 p.Gln1756.Profs*74)与MDA-MB-231和T47D BRCA1/2野生型乳腺癌细胞株的特性。从一组BRCA1/2-野生型患者的抽脂液中培养ADSCs。使用增殖和迁移实验以及脂肪因子表达western blot阵列研究了这些细胞在条件培养基(CM)中与乳腺癌细胞系的相互作用。ADSCs的CM对乳腺癌细胞系的增殖有剂量依赖性的刺激作用。然而,在测试的ADSC制剂中,18个样品中只有1个样品对brca1突变的MDA-MB-436细胞的刺激作用明显高于野生型MDA-MB-231细胞,所有CM对brca1突变的HCC1937细胞的刺激作用均低于野生型T47D细胞。此外,BRCA1/2突变的乳腺癌细胞对ADSCs的迁移反应与未突变的癌细胞相当或更慢,并且除了血管生成素样2外,诱导的脂肪因子表达没有显着差异。正常ADSCs调节的培养基对brca1突变和野生型乳腺癌细胞系的作用大致相当,因此提倡脂质填充,优先使用同种异体未突变的ADSCs。
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Interactions of BRCA1-mutated Breast Cancer Cell Lines with Adipose-derived Stromal Cells (ADSCs).

Lipofilling may constitute a technique to assist reconstruction of breasts following prophylactic mastectomy for patients with mutated BRCA1 or BRCA2 genes. However, to date it is not clear whether adipose-derived stromal cells (ADSCs) increase the risk of tumor initiation and progression in this situation. Therefore, the interactions of BRCA1 mutated breast cancer cell lines with normal ADSCs were investigated in the present study. Characteristics of MDA-MB-436 (BRCA1 c.5277 + 1G > A) and HCC1937 (BRCA1 p.Gln1756.Profs*74) were compared to MDA-MB-231 and T47D BRCA1/2 wild-type breast cancer cell lines. ADSCs were cultivated from lipoaspirates of a panel of BRCA1/2- wildtype patients. Interactions of conditioned medium (CM) of these cells with the breast cancer lines were studied using proliferation and migration assays as well as adipokine expression western blot arrays. CM of ADSCs exhibit a dose-dependent stimulation of the proliferation of the breast cancer cell lines. However, of the ADSC preparations tested, only 1 out of 18 samples showed a significant higher stimulation of BRCA1-mutated MDA-MB-436 versus wildtype MDA-MB-231 cells, and all CM revealed lower stimulatory activity for BRCA1-mutated HCC1937 versus wildtype T47D cells. Additionally, migration of breast cancer cells in response to CM of ADSCs proved to be equivalent or slower for BRCA1/2 mutated versus nonmutated cancer cells and, with exception of angiopoietin-like 2, induced expression of adipokines showed no major difference. Effects of media conditioned by normal ADSCs showed largely comparable effects on BRCA1-mutated and wildtype breast cancer cell lines thus advocating lipofilling, preferentially employing allogeneic non-mutated ADSCs.

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来源期刊
Journal of Mammary Gland Biology and Neoplasia
Journal of Mammary Gland Biology and Neoplasia 医学-内分泌学与代谢
CiteScore
5.30
自引率
4.00%
发文量
22
期刊介绍: Journal of Mammary Gland Biology and Neoplasia is the leading Journal in the field of mammary gland biology that provides researchers within and outside the field of mammary gland biology with an integrated source of information pertaining to the development, function, and pathology of the mammary gland and its function. Commencing in 2015, the Journal will begin receiving and publishing a combination of reviews and original, peer-reviewed research. The Journal covers all topics related to the field of mammary gland biology, including mammary development, breast cancer biology, lactation, and milk composition and quality. The environmental, endocrine, nutritional, and molecular factors regulating these processes is covered, including from a comparative biology perspective.
期刊最新文献
Gestational breast cancer: distinctive molecular and clinico-epidemiological features. Intramammary Labeling of Epithelial Cell Division. Immune Cell Contribution to Mammary Gland Development. Perimenopausal and Menopausal Mammary Glands In A 4-Vinylcyclohexene Diepoxide Mouse Model. State of the Art Modelling of the Breast Cancer Metastatic Microenvironment: Where Are We?
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