Ponzetti Marco, Capulli Mattia, Angelucci Adriano, Ventura Luca, Monache Simona Delle, Mercurio Cinzia, Calgani Alessia, Sanità Patrizia, Teti Anna, Rucci Nadia
Department of Biotechnological and Applied Clinical Sciences, University of L'Aquila, L'Aquila, Italy.
Department of Pathology, San Salvatore Hospital, L'Aquila, Italy.
Br J Cancer. 2017 Sep 26;117(7):994-1006. doi: 10.1038/bjc.2017.247. Epub 2017 Aug 3.
Besides its role as oxygen transporter, recent findings suggest that haemoglobin beta (HBB) may have roles in other contexts.
We evaluated the impact of HBB expression in primary human breast cancers, and in breast cancer cell lines overexpressing HBB by in vitro and in vivo studies. Publicly available microarray databases were used to perform multivariate survival analyses.
A significantly higher expression of HBB was observed in invasive carcinoma histotypes vs in situ counterparts, along with a positive correlation between HBB and the Ki67 proliferation marker. HBB-overexpressing breast cancer cells migrate and invade more, show HIF-1α upregulation and their conditioned media enhances angiogenesis. Blocking the oxygen-binding site of HBB reverts the increase of migration and HIF-1α upregulation observed in HBB-overexpressing breast cancer cells. Orthotopically implanted MDA-MB-231 overexpressing HBB (MDA-HBB) generated tumours with faster growth rate and increased neoangiogenesis. Moreover, local recurrence and visceral metastases were observed only in MDA-HBB-implanted mice. Similar results were observed with 4T1 mouse breast cancer cells. Finally, bioinformatics analyses of public data sets correlated high HBB expression with lower overall survival.
HBB expression increases breast cancer cells aggressiveness and associates with poor prognosis, pointing to HBB as a novel biomarker for breast cancer progression.
除了作为氧转运蛋白的作用外，最近的研究结果表明血红蛋白β（HBB）可能在其他情况下也发挥作用。
我们通过体外和体内研究评估了HBB在原发性人类乳腺癌以及过表达HBB的乳腺癌细胞系中的表达影响。利用公开可用的微阵列数据库进行多变量生存分析。
与原位癌相比，浸润性癌组织学类型中观察到HBB表达显著更高，并且HBB与Ki67增殖标志物之间呈正相关。过表达HBB的乳腺癌细胞迁移和侵袭能力更强，显示HIF-1α上调，其条件培养基可增强血管生成。阻断HBB的氧结合位点位点位点可逆转过表达HBB的乳腺癌细胞中观察到的迁移增加和HIF-1α上调。原位植入过表达HBB的MDA-MB-231（MDA-HBB）产生的肿瘤生长速度更快，新生血管生成增加。此外，仅在植入MDA-HBB的小鼠中观察到局部复发和内脏转移。用4T1小鼠乳腺癌细胞也观察到了类似结果。最后，对公共数据集的生物信息学分析将高HBB表达与较低的总生存率相关联。
HBB表达增加乳腺癌细胞的侵袭性并与不良预后相关，表明HBB是乳腺癌进展的一种新型生物标志物。
