独立于肥胖状态的脂肪细胞诱导逃离人造人乳腺微瘤

IF 2.3 4区 医学 Q3 BIOPHYSICS Cellular and molecular bioengineering Pub Date : 2022-12-09 eCollection Date: 2023-02-01 DOI:10.1007/s12195-022-00750-y
Yoseph W Dance, Mackenzie C Obenreder, Alex J Seibel, Tova Meshulam, Joshua W Ogony, Nikhil Lahiri, Laura Pacheco-Spann, Derek C Radisky, Matthew D Layne, Stephen R Farmer, Celeste M Nelson, Joe Tien
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引用次数: 0

摘要

引言肥胖与乳腺癌发病率、复发率和死亡率的增加有关。脂肪细胞和脂肪衍生干细胞(ASCs)是脂肪组织中的两种常住细胞类型,可加速乳腺癌的早期发展。目前仍不清楚肥胖是否在恶性乳腺癌细胞随后逃逸到局部循环中发挥作用:方法:我们设计了具有不同肥胖特异性改变的脂肪基质的人类乳腺肿瘤模型。我们用这些模型评估了乳腺癌细胞在长达 16 天的时间里向空的盲端空腔(模拟淋巴管)的侵袭和逃逸情况:结果:瘦弱和肥胖的供体脂肪基质加速逃逸的程度相似。此外,肥厚的脂肪基质不会影响脂肪诱导逸出的速度。当将瘦和肥胖供体来源的间充质干细胞直接混入模型肿瘤时,它们加速逃逸的程度相似:这项研究表明,在多种肥胖相关乳腺癌模型中,脂肪细胞的存在(与脂肪组织供体的肥胖状况无关)会加速人类乳腺癌细胞的逃逸:在线版本包含补充材料,可在 10.1007/s12195-022-00750-y.获取。
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Adipose Cells Induce Escape from an Engineered Human Breast Microtumor Independently of their Obesity Status.

Introduction: Obesity is associated with increased breast cancer incidence, recurrence, and mortality. Adipocytes and adipose-derived stem cells (ASCs), two resident cell types in adipose tissue, accelerate the early stages of breast cancer progression. It remains unclear whether obesity plays a role in the subsequent escape of malignant breast cancer cells into the local circulation.

Methods: We engineered models of human breast tumors with adipose stroma that exhibited different obesity-specific alterations. We used these models to assess the invasion and escape of breast cancer cells into an empty, blind-ended cavity (as a mimic of a lymphatic vessel) for up to sixteen days.

Results: Lean and obese donor-derived adipose stroma hastened escape to similar extents. Moreover, a hypertrophic adipose stroma did not affect the rate of adipose-induced escape. When admixed directly into the model tumors, lean and obese donor-derived ASCs hastened escape similarly.

Conclusions: This study demonstrates that the presence of adipose cells, independently of the obesity status of the adipose tissue donor, hastens the escape of human breast cancer cells in multiple models of obesity-associated breast cancer.

Supplementary information: The online version contains supplementary material available at 10.1007/s12195-022-00750-y.

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来源期刊
CiteScore
5.60
自引率
3.60%
发文量
30
审稿时长
>12 weeks
期刊介绍: The field of cellular and molecular bioengineering seeks to understand, so that we may ultimately control, the mechanical, chemical, and electrical processes of the cell. A key challenge in improving human health is to understand how cellular behavior arises from molecular-level interactions. CMBE, an official journal of the Biomedical Engineering Society, publishes original research and review papers in the following seven general areas: Molecular: DNA-protein/RNA-protein interactions, protein folding and function, protein-protein and receptor-ligand interactions, lipids, polysaccharides, molecular motors, and the biophysics of macromolecules that function as therapeutics or engineered matrices, for example. Cellular: Studies of how cells sense physicochemical events surrounding and within cells, and how cells transduce these events into biological responses. Specific cell processes of interest include cell growth, differentiation, migration, signal transduction, protein secretion and transport, gene expression and regulation, and cell-matrix interactions. Mechanobiology: The mechanical properties of cells and biomolecules, cellular/molecular force generation and adhesion, the response of cells to their mechanical microenvironment, and mechanotransduction in response to various physical forces such as fluid shear stress. Nanomedicine: The engineering of nanoparticles for advanced drug delivery and molecular imaging applications, with particular focus on the interaction of such particles with living cells. Also, the application of nanostructured materials to control the behavior of cells and biomolecules.
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