甲状腺滤泡细胞上皮-间质转化的诱导与细胞粘附改变和低剂量超辐射敏感性有关。

Q3 Biochemistry, Genetics and Molecular Biology

Tumor Biology Pub Date : 2023-01-01 DOI:10.3233/TUB-220027

Ankit Mathur, Vijayakumar Chinnadurai, Param Jit Singh Bhalla, Sudhir Chandna

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引用次数: 0

摘要

背景：上皮-间充质转化（EMT）与细胞粘附的改变有关。我们之前已经证明，细胞粘附会影响各种肿瘤细胞的低剂量超辐射敏感性（HRS）。然而，低剂量HRS与EMT在肿瘤转化过程中引起的表型可塑性的关系仍有待阐明。目的：探讨在进行性肿瘤转化过程中获得EMT表型是否会影响低剂量辐射敏感性。方法：首先对从人类囊性甲状腺结节中获得的原代甲状腺细胞进行营养应激。这产生了永生化的INM-Thy1细胞株，该细胞株用多种γ-辐射组分（1.5 Gy）或3-甲基胆蒽和佛波醇-12-嘧啶酸酯-13-乙酸酯的重复循环，产生两个渐进转化体，即INM-Thy1R和INM-Thy1C。对这些菌株的形态学改变、染色体双分钟、细胞粘附蛋白、锚定依赖性、裸鼠致瘤性和细胞放射敏感性进行了研究。结果：两个转化体（INM-Thy1R、INM-Thy1C）均表现出进行性致瘤特征，即在裸鼠体内软琼脂集落生长和实体瘤生长，并伴有上皮-间充质转化和激活Wnt途径的特征。顺便说一句，化学诱导的转化体（INM-Thy1C）显示出显著的HRS（αs/αr=29.35），在高细胞密度下不受影响。然而，亲代（INM-Thy1）细胞系以及辐射诱导的转化体（INM-Thy1R）未能表现出这种超敏反应。结论：研究表明，EMT在甲状腺滤泡细胞中的诱导可能伴随着对低剂量电离辐射的易感性增加，而在辐射诱导的转化过程中获得的适应性抗性减弱了这种易感性。

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Induction of epithelial-mesenchymal transition in thyroid follicular cells is associated with cell adhesion alterations and low-dose hyper-radiosensitivity.

Background: Epithelial-mesenchymal transition (EMT) is associated with altered cellular adhesion. We previously demonstrated that cellular adhesion influences Low-dose Hyper-Radiosensitivity (HRS) in a variety of tumor cells. However, the relationship of low-dose HRS with the phenotypic plasticity incurred by EMT during the neoplastic transformation remains to be elucidated.

Objective: To investigate whether acquisition of EMT phenotype during progressive neoplastic transformation may affect low-dose radiation sensitivity.

Methods: Primary thyroid cells obtained from a human cystic thyroid nodule were first subjected to nutritional stress. This yielded immortalized INM-Thy1 cell strain, which was further treated with either multiple γ-radiation fractions (1.5 Gy each) or repetitive cycles of 3-methylcholanthrene and phorbol-12-myristate-13-acetate, yielding two progressive transformants, viz., INM-Thy1R and INM-Thy1C. Morphological alterations, chromosomal double-minutes, cell adhesion proteins, anchorage dependency, tumorigenicity in nude mice and cellular radiosensitivity were studied in these strains.

Results: Both transformants (INM-Thy1R, INM-Thy1C) displayed progressive tumorigenic features, viz., soft agar colony growth and solid tumor growth in nude mice, coupled with features of epithelial-mesenchymal transition and activated Wnt pathway. Incidentally, the chemical-induced transformant (INM-Thy1C) displayed a prominent HRS (αs/αr = 29.35) which remained unaffected at high cell density. However, the parental (INM-Thy1) cell line as well as radiation-induced transformant (INM-Thy1R) failed to show this hypersensitivity.

Conclusion: The study shows that induction of EMT in thyroid follicular cells may accompany increased susceptibility to low-dose ionizing radiation, which was attenuated by adaptive resistance acquired during radiation-induced transformation.

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来源期刊

Tumor Biology 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

审稿时长

1 months

期刊介绍： Tumor Biology is a peer reviewed, international journal providing an open access forum for experimental and clinical cancer research. Tumor Biology covers all aspects of tumor markers, molecular biomarkers, tumor targeting, and mechanisms of tumor development and progression. Specific topics of interest include, but are not limited to: Pathway analyses, Non-coding RNAs, Circulating tumor cells, Liquid biopsies, Exosomes, Epigenetics, Cancer stem cells, Tumor immunology and immunotherapy, Tumor microenvironment, Targeted therapies, Therapy resistance Cancer genetics, Cancer risk screening. Studies in other areas of basic, clinical and translational cancer research are also considered in order to promote connections and discoveries across different disciplines. The journal publishes original articles, reviews, commentaries and guidelines on tumor marker use. All submissions are subject to rigorous peer review and are selected on the basis of whether the research is sound and deserves publication. Tumor Biology is the Official Journal of the International Society of Oncology and BioMarkers (ISOBM).