Laboratorio de Inmuno-Hematología, Instituto de Biología y Medicina Experimental (IBYME), Buenos Aires, Argentina.
Cancer Cell Int. 2012 Jun 18;12(1):29. doi: 10.1186/1475-2867-12-29.
While breast cancer (BC) is the major cause of death among women worldwide, there is no guarantee of better patient survival because many of these patients develop primarily metastases, despite efforts to detect it in its early stages. Bone metastasis is a common complication that occurs in 65-80 % of patients with disseminated disease, but the molecular basis underlying dormancy, dissemination and establishment of metastasis is not understood. Our objective has been to evaluate simultaneously osteoprotegerin (OPG), receptor activator of nuclear factor kappa B ligand (RANKL), tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), stromal cell-derived factor-1 (SDF-1), and their receptors (R) in 2 human BC cell lines, MDA-MB-231 and MCF-7.
OPG, RANKL, TRAIL and SDF-1 expression and release, in addition to the expression of their receptors has been investigated using immunofluorescence, immunocytochemistry and ELISA analyses.
MCF-7 cells released higher levels of OPG in conditioned media (CM) than MDA-MB-231 cells; 100 % of both types of cell expressed OPG, RANKL, TRAIL and SDF-1. Moreover, 100 % in both lines expressed membrane RANKL and RANK, whereas only 50 % expressed CXCR4. Furthermore, 100 % expressed TRAIL-R1 and R4, 30-50 % TRAIL-R2, and 40-55 % TRAIL-R3.
MCF-7 and MDA-MB-231 cells not only released OPG, but expressed RANKL, TRAIL and SDF-1. The majority of the cells also expressed RANK, CXCR4 and TRAIL-R. Since these ligands and their receptors are implicated in the regulation of proliferation, survival, migration and future bone metastasis during breast tumor progression, assessment of these molecules in tumor biopsies of BC patients could be useful in identifying patients with more aggressive tumors that are also at risk of bone metastasis, which may thus improve the available options for therapeutic intervention.
虽然乳腺癌（BC）是全球女性死亡的主要原因，但由于许多患者尽管努力在早期发现，但仍主要发展为转移，因此并不能保证患者的生存得到改善。骨转移是一种常见的并发症，发生在 65-80%的播散性疾病患者中，但休眠、传播和转移建立的分子基础尚不清楚。我们的目标是同时评估 2 个人乳腺癌细胞系 MDA-MB-231 和 MCF-7 中的骨保护素（OPG）、核因子 kappa B 配体受体激活剂（RANKL）、肿瘤坏死因子相关凋亡诱导配体（TRAIL）、基质细胞衍生因子-1（SDF-1）及其受体（R）。
使用免疫荧光、免疫细胞化学和 ELISA 分析研究了 OPG、RANKL、TRAIL 和 SDF-1 的表达和释放，以及它们的受体表达。
与 MDA-MB-231 细胞相比，MCF-7 细胞在条件培养基（CM）中释放更高水平的 OPG；两种类型的细胞均 100%表达 OPG、RANKL、TRAIL 和 SDF-1。此外，两种细胞系均 100%表达膜 RANKL 和 RANK，而仅 50%表达 CXCR4。此外，100%表达 TRAIL-R1 和 R4，30-50%表达 TRAIL-R2，40-55%表达 TRAIL-R3。
MCF-7 和 MDA-MB-231 细胞不仅释放 OPG，而且还表达 RANKL、TRAIL 和 SDF-1。大多数细胞还表达 RANK、CXCR4 和 TRAIL-R。由于这些配体及其受体参与调节乳腺癌肿瘤进展过程中的增殖、存活、迁移和未来骨转移，因此评估 BC 患者肿瘤活检中的这些分子可能有助于识别具有更具侵袭性肿瘤的患者，这些患者也有发生骨转移的风险，从而改善现有的治疗干预选择。
