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自发性破骨细胞生成,晚期腔面A型乳腺癌患者发生骨转移的一个风险因素。

Spontaneous Osteoclastogenesis, a risk factor for bone metastasis in advanced luminal A-type breast cancer patients.

作者信息

Fernández Vallone Valeria, Borzone Francisco Raúl, Martinez Leandro Marcelo, Giorello María Belén, Choi Hosoon, Dimase Federico, Feldman Leonardo, Bordenave Raúl Horacio, Chudzinski-Tavassi Ana Marisa, Batagelj Emilio, Chasseing Norma Alejandra

机构信息

Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Core Unit Pluripotent Stem Cells and Organoids, Berlin, Germany.

Laboratorio de Inmunohematología, Instituto de Biología y Medicina Experimental (IBYME), Consejo Nacional de Investigaciones Científicas y Técnicas (CONICET), Buenos Aires, Argentina.

出版信息

Front Oncol. 2023 Feb 20;13:1073793. doi: 10.3389/fonc.2023.1073793. eCollection 2023.

Abstract

INTRODUCTION

Osteolytic bone metastasis in advanced breast cancer stages are a major complication for patient´s quality life and a sign of low survival prognosis. Permissive microenvironments which allow cancer cell secondary homing and later proliferation are fundamental for metastatic processes. The causes and mechanisms behind bone metastasis in breast cancer patients are still an unsolved puzzle. Therefore, in this work we contribute to describe bone marrow pre-metastatic niche in advanced breast cancer patients.

RESULTS

We show an increase in osteoclasts precursors with a concomitant imbalance towards spontaneous osteoclastogenesis which can be evidenced at bone marrow and peripheral levels. Pro-osteoclastogenic factors RANKL and CCL-2 may contribute to bone resorption signature observed in bone marrow. Meanwhile, expression levels of specific microRNAs in primary breast tumors may already indicate a pro-osteoclastogenic scenario prior to bone metastasis.

DISCUSSION

The discovery of prognostic biomarkers and novel therapeutic targets linked to bone metastasis initiation and development are a promising perspective for preventive treatments and metastasis management in advanced breast cancer patients.

摘要

引言

晚期乳腺癌阶段的溶骨性骨转移是影响患者生活质量的主要并发症,也是生存预后不良的标志。允许癌细胞继发性归巢并随后增殖的宽松微环境是转移过程的基础。乳腺癌患者骨转移背后的原因和机制仍是未解之谜。因此,在这项研究中,我们致力于描述晚期乳腺癌患者骨髓中的前转移微环境。

结果

我们发现破骨细胞前体增加,同时自发性破骨细胞生成出现失衡,这在骨髓和外周水平均可得到证实。促破骨细胞生成因子RANKL和CCL-2可能导致骨髓中观察到的骨吸收特征。与此同时,原发性乳腺肿瘤中特定微小RNA的表达水平可能在骨转移之前就已表明存在促破骨细胞生成的情况。

讨论

发现与骨转移起始和发展相关的预后生物标志物和新型治疗靶点,对于晚期乳腺癌患者的预防性治疗和转移管理而言是一个充满希望的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6fe9/9986318/bb4cb3fc3452/fonc-13-1073793-g001.jpg

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