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Proteomic identification of tumor- and metastasis-associated galectin-1 in claudin-low breast cancer
Biochimica et Biophysica Acta (BBA) - General Subjects ( IF 3 ) Pub Date : 2020-11-07 , DOI: 10.1016/j.bbagen.2020.129784
Kassondra Balestrieri , Kimberly Kew , Moses McDaniel , Mohamed Ramez , H. Keith Pittman , Gina Murray , Nasreen A. Vohra , Kathryn M. Verbanac

Background

Metastasis and mortality remain high among breast cancer patients with the claudin-low subtype because these tumors are aggressive, chemoresistant, and lack targeted therapies. Our objective was to utilize discovery-based proteomics to identify proteins associated with claudin-low primary and metastatic tumors to gain insight into pathways and mechanisms of tumor progression.

Methods

We used nano-LC-MS/MS proteomics to analyze orthotopic and metastatic tumors from the syngeneic murine T11 tumor model, which displays gene expression profiles mirroring human claudin-low tumors. Galectin-1 identity, expression and spatial distribution were investigated by biochemical and immunochemical methods and MALDI/IMS. RNA seq data from mouse and human tumors in our study and publicly available microarray data were analyzed for differential galectin-1 expression across breast cancer subtypes.

Results

Galectin-1, an N-acetyllactosamine-binding protein, exhibited the highest sequence coverage and high abundance rank order among nano-LC-MS/MS-identified proteins shared by T11 claudin-low tumors but not normal tissue. Label-free quantitation, Western immunoblot and ELISA confirmed galectin-1 identity and significant differential expression. MALDI/IMS spatial mapping and immunohistochemistry detected galectin-1 in T11 metastatic lung foci. Immunohistochemistry of human claudin-low tumors demonstrated intermediate-to-high intensity galectin-1 staining of tumor and stroma. Gene expression analysis of mouse and human tumors found the highest galectin-1 levels in the claudin-low breast cancer subtype.

Conclusions

Proteomics and genomics reveal high expression of galectin-1 protein and RNA in primary and metastatic claudin-low breast cancer.

General significance

This work endorses proteomic approaches in cancer research and supports further investigations of the function and significance of galectin-1 overexpression in claudin-low tumor progression.



中文翻译:

蛋白质组学鉴定claudin低位乳腺癌中与肿瘤和转移相关的galectin-1

背景

在claudin-低亚型的乳腺癌患者中,转移和死亡率仍然很高,因为这些肿瘤具有侵袭性,化学抗性并且缺乏靶向治疗。我们的目标是利用基于发现的蛋白质组学来鉴定与claudin低原发性和转移性肿瘤相关的蛋白质,以深入了解肿瘤进展的途径和机制。

方法

我们使用了纳米LC-MS / MS蛋白质组学技术,从同系鼠T11肿瘤模型中分析了原位和转移性肿瘤,该模型显示了与人claudin低肿瘤相似的基因表达谱。通过生化和免疫化学方法以及MALDI / IMS研究了Galectin-1的身份,表达和空间分布。在我们的研究中,来自小鼠和人类肿瘤的RNA seq数据以及可公开获得的微阵列数据分析了乳腺癌亚型之间不同的galectin-1表达。

结果

Galectin-1是一种N-乙酰基乳糖胺结合蛋白,在纳米LC-MS / MS鉴定的T11 claudin低肿瘤(而非正常组织)共有的蛋白中,具有最高的序列覆盖率和高丰度等级顺序。无标记定量,Western免疫印迹和ELISA证实了Galectin-1的身份和明显的差异表达。MALDI / IMS空间定位和免疫组织化学检测到T11转移性肺灶中的半乳凝素-1。人类claudin低型肿瘤的免疫组织化学显示,肿瘤和基质的中高强度galectin-1染色呈中等至高强度。小鼠和人类肿瘤的基因表达分析发现,在claudin-low乳腺癌亚型中,galectin-1水平最高。

结论

蛋白质组学和基因组学揭示了半乳糖凝集素-1蛋白和RNA在原发性和转移性克劳丁低乳腺癌中的高表达。

一般意义

这项工作支持蛋白质组学方法在癌症研究中的应用,并支持进一步研究半乳糖凝集素-1低表达在claudin低肿瘤进展中的功能和意义。

更新日期:2020-12-01
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