IMP3免疫组织化学表达与异种移植和皮肤黑色素瘤的进展和转移有关。

IF 3.5 4区 医学 Q3 CELL BIOLOGY Pathobiology Pub Date : 2024-01-01 Epub Date: 2023-10-05 DOI:10.1159/000533916
Natividad Martin-Morales, Miguel Padial-Molina, Isabel Tovar, Virginea De Araujo Farias, Pedro Hernández-Cortés, Esperanza Ramirez-Moreno, Mercedes Caba-Molina, Justin Davis, Alejandro Carrero Castaño, Jose Mariano Ruiz de Almodovar, Pablo Galindo-Moreno, Javier Oliver-Pozo, Francisco Javier O'Valle Ravassa
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引用次数: 0

摘要

引言:胰岛素样生长因子II信使RNA(mRNA)结合蛋白-3(IMP3)的过度表达是某些类型人类黑色素瘤肿瘤复发和转移的预测因素。我们的目的是评估正在接受治疗的黑色素瘤异种肿瘤中IMP3和其他与肿瘤预后相关的分子的免疫组织化学表达。材料和方法:将A375和G361人黑色素瘤细胞系接种到NOD/SCIDγ小鼠体内。我们评估了IMP3、E-钙粘蛋白、N-钙粘蛋白,PARP1、HIF-1α和增殖标志物Ki-67的免疫组织化学表达。此外,我们进行了一项回顾性研究,包括114例被诊断为恶性皮肤浅表扩散性黑色素瘤和结节性黑色素癌的患者的组织学样本,并进行了至少五年的随访。结果:大多数形态学和免疫组化特征显示,这两种细胞系之间存在统计学上的显著差异。所有三种治疗都降低了Ki-67核抗原评估的细胞增殖(P=0.000),并减少了转移数量(P=0.004)。此外,与对照组相比,肿瘤体积减少,A357肿瘤细胞系中RT+MSCs减少了31.74%,G361肿瘤细胞系的RT+MSC减少了89.84%。我们还发现IMP3的表达与更大的肿瘤侵袭性有关,并且与细胞增殖、转移数量和粘附分子表达减少显著相关。讨论/结论:RT+MSCs联合治疗异种移植黑色素瘤可降低肿瘤大小、转移频率和EMT/PARP1转移表型。这种治疗还降低了与细胞增殖相关的分子(Ki-67)、促进转移过程的分子(E-钙粘蛋白)和与预后相关的分子的表达(IMP3)。
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IMP3 Immunohistochemical Expression Is Related with Progression and Metastases in Xenografted and Cutaneous Melanomas.

Introduction: Insulin-like growth factor-II messenger RNA-binding protein-3 (IMP3) over-expression is a predictor of tumor recurrence and metastases in some types of human melanoma. Our objective was to evaluate the immunohistochemical expression of IMP3 and other molecules related to tumor prognosis in melanoma-xeno-tumors undergoing treatment. We test the effect of radiotherapy (RT) and mesenchymal stromal cells (MSCs) treatment, analyzing the tumorigenic and metastatsizing capacity in a mice melanoma xenograft model.

Materials and methods: We inoculated A375 and G361 human melanoma cell lines into NOD/SCID gamma mice (n = 64). We established a control group, a group treated with MSCs, a group treated with MSCs plus RT, and a group treated with RT. We assessed the immunohistochemical expression of IMP3, E-cadherin, N-cadherin, PARP1, HIF-1α, and the proliferation marker Ki-67. Additionally, we performed a retrospective study including 114 histological samples of patients diagnosed with malignant cutaneous superficial spreading melanoma (n = 104) and nodular melanoma (n = 10) with at least 5 years of follow-up.

Results: Most morphological and immunohistochemical features show statistically significant differences between the 2 cell lines. The A375 cell line induced the formation of metastases, while the G361 cell line provoked tumor formation but not metastases. All three treatments reduced the cell proliferation evaluated by the Ki-67 nuclear antigen (p = 0.000, one-way ANOVA test) and reduced the number of metastases (p = 0.004, one-way ANOVA test). In addition, the tumor volumes reduced in comparison with the control groups, 31.74% for RT + MSCs in the A357 tumor cell line, and 89.84% RT + MSCs in the G361 tumor cell line. We also found that IMP3 expression is associated with greater tumor aggressiveness and was significantly correlated with cell proliferation (measured by the expression of Ki-67), the number of metastases, and reduced expression of adhesion molecules.

Conclusions: The combined treatment of RT and MSCs on xenografted melanomas reduces tumor size, metastases frequency, and the epithelial to mesenchymal transition/PARP1 metastatic phenotype. This treatment also reduces the expression of molecules related to cellular proliferation (Ki-67), molecules that facilitate the metastatic process (E-cadherin), and molecules related with prognosis (IMP3).

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来源期刊
Pathobiology
Pathobiology 医学-病理学
CiteScore
8.50
自引率
0.00%
发文量
47
审稿时长
>12 weeks
期刊介绍: ''Pathobiology'' offers a valuable platform for the publication of high-quality original research into the mechanisms underlying human disease. Aiming to serve as a bridge between basic biomedical research and clinical medicine, the journal welcomes articles from scientific areas such as pathology, oncology, anatomy, virology, internal medicine, surgery, cell and molecular biology, and immunology. Published bimonthly, ''Pathobiology'' features original research papers and reviews on translational research. The journal offers the possibility to publish proceedings of meetings dedicated to one particular topic.
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