Human breast tumor derived endothelial cells exhibit distinct biological properties

IF 2.4 4区生物学 Q4 CELL BIOLOGY

Biology of the Cell Pub Date : 2021-11-10 DOI:10.1111/boc.202100015

Mangala Hegde, Sharath Mohan Bhat, Kanive Parashiva Guruprasad, Rajasekhar Moka, Lingadakai Ramachandra, Kapaettu Satyamoorthy, Manjunath B. Joshi

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引用次数: 3

Abstract

Background Information

Excessive angiogenesis characterized by leaky, tortuous, and chaotic vasculature is one of the hallmarks of cancers and is significantly correlated to poor prognosis. Disorganized angiogenesis leads to poor perfusion of anti-cancer drugs and limits access to immune cells. Hence, impeding angiogenesis is one of the attractive therapeutic targets to inhibit progression and metastasis in several solid tumors including breast.

Results

We have developed a robust and reproducible method for isolating and ex vivo culture of endothelial cells (EC) derived from non-malignant (Endo-N) and malignant (Endo-T) part from clinically characterized human breast tumors. RT-PCR and immunoblotting analysis indicated that these cells exhibited expression of endothelial specific genes such as PECAM-1 (CD31), Endoglin (CD105), eNOS, VE-cadherin, VCAM1, and MCAM. Vasculogenic mimicry and contamination of progenitor EC recruited in tumors was ruled out by absence of CD133 expression and normal karyotype. Both the cell types showed stable expression of CD31 and CD105 up to seven passages. Furthermore, compared to Endo-N cells, Endo-T cells showed (a) constitutively increased proliferation marked by nearly 36% of cells in mitotic phase, (b) requirement of glutamine for cell survival, (c) pro-migratory phenotype, (d) produced increased number of sprouts in 3D cultures, and (e) resistance to sorafenib.

Conclusion

Tumor derived EC showed distinct biological properties compared to normal breast EC.

Significance

Our method for isolating endothelial cell types from human breast tumors may be explored to (a) understand cellular and molecular mechanisms, (b) screen anti-angiogenic molecules, and (c) formulate organoid cultures to develop personalized medicine facilitating better clinical management of breast cancers.

Abstract Image

查看原文本刊更多论文

人类乳腺肿瘤衍生的内皮细胞表现出不同的生物学特性。

血管生成过多，血管渗漏、扭曲、混乱是癌症的标志之一，与预后不良有显著关系。血管生成紊乱导致抗癌药物灌注不良，限制了免疫细胞的进入。因此，阻碍血管生成是抑制包括乳腺在内的多种实体肿瘤进展和转移的有吸引力的治疗靶点之一。结果我们开发了一种可靠且可重复的方法，用于分离和体外培养来自临床特征的人乳腺肿瘤非恶性(Endo-N)和恶性(Endo-T)部分的内皮细胞(EC)。RT-PCR和免疫印迹分析表明，这些细胞表达内皮特异性基因，如PECAM-1 (CD31)、Endoglin (CD105)、eNOS、VE-cadherin、VCAM1和MCAM。由于缺乏CD133表达和正常核型，排除了肿瘤中招募的血管源性模仿和祖细胞EC污染。两种细胞类型在7代内均能稳定表达CD31和CD105。此外，与ento - n细胞相比，ento - t细胞表现出(a)有丝分裂期近36%的细胞增殖增加，(b)细胞存活需要谷氨酰胺，(c)亲迁移表型，(d)在3D培养中产生更多芽，(e)对索拉非尼耐药。结论肿瘤源性乳糜泻与正常乳腺乳糜泻具有明显的生物学特性。我们从人乳腺肿瘤中分离内皮细胞类型的方法可以探索(a)了解细胞和分子机制，(b)筛选抗血管生成分子，以及(c)制定类器官培养以开发个性化药物，促进更好的乳腺癌临床管理。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Biology of the Cell 生物-细胞生物学

CiteScore

5.30

自引率

0.00%

发文量

审稿时长

>12 weeks

期刊介绍： The journal publishes original research articles and reviews on all aspects of cellular, molecular and structural biology, developmental biology, cell physiology and evolution. It will publish articles or reviews contributing to the understanding of the elementary biochemical and biophysical principles of live matter organization from the molecular, cellular and tissues scales and organisms. This includes contributions directed towards understanding biochemical and biophysical mechanisms, structure-function relationships with respect to basic cell and tissue functions, development, development/evolution relationship, morphogenesis, stem cell biology, cell biology of disease, plant cell biology, as well as contributions directed toward understanding integrated processes at the organelles, cell and tissue levels. Contributions using approaches such as high resolution imaging, live imaging, quantitative cell biology and integrated biology; as well as those using innovative genetic and epigenetic technologies, ex-vivo tissue engineering, cellular, tissue and integrated functional analysis, and quantitative biology and modeling to demonstrate original biological principles are encouraged.