Non-conventional role of haemoglobin beta in breast malignancy.
Non-conventional role of haemoglobin beta in breast malignancy.
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DOI：
10.1038/bjc.2017.247
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发表时间：
2017-09-26
影响因子：
8.8
通讯作者：
Rucci N
中科院分区：
文献类型：
--
作者：
Ponzetti M;Capulli M;Angelucci A;Ventura L;Monache SD;Mercurio C;Calgani A;Sanità P;Teti A;Rucci N
除了作为氧转运体的作用外，最近的研究结果表明血红蛋白β (HBB)可能在其他情况下也有作用。我们通过体外和体内研究评估了HBB在原发性人类乳腺癌中的表达，以及在过表达HBB的乳腺癌细胞系中的影响。使用公开可用的微阵列数据库进行多变量生存分析。侵袭性癌组织型中HBB的表达明显高于原位癌组织型，且HBB与Ki67增殖标志物呈正相关。过表达hbb的乳腺癌细胞迁移和侵袭性增强，HIF-1α表达上调，条件培养基促进血管生成。阻断HBB的氧结合位点可以逆转HBB过表达乳腺癌细胞中迁移和HIF-1α上调的增加。原位植入过表达HBB的MDA-MB-231 （MDA-HBB）后，肿瘤生长速度加快，新生血管生成增加。此外，仅在mda - hbb植入小鼠中观察到局部复发和内脏转移。在4T1小鼠乳腺癌细胞中也观察到类似的结果。最后，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联系起来。HBB的表达增加了乳腺癌细胞的侵袭性，并与不良预后相关，这表明HBB是乳腺癌进展的一种新的生物标志物。
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.
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DOI：
10.2147/hp.s50651
发表时间：
2014
期刊：
Hypoxia (Auckland, N.Z.)
影响因子：
--
作者：
Tiburcio PD;Choi H;Huang LE
通讯作者：
Huang LE
影响因子：
2.8
作者：
Courtnay, Rupert;Ngo, Darleen C.;Karagiannis, Tom C.
通讯作者：
Karagiannis, Tom C.
DOI：
10.1073/pnas.96.12.6643
发表时间：
1999-06-08
影响因子：
11.1
作者：
Liu, LM;Zeng, M;Stamler, JS
通讯作者：
Stamler, JS
影响因子：
14.9
作者：
Franceschini A;Szklarczyk D;Frankild S;Kuhn M;Simonovic M;Roth A;Lin J;Minguez P;Bork P;von Mering C;Jensen LJ
通讯作者：
Jensen LJ
DOI：
10.1016/j.bbrc.2005.06.042
发表时间：
2005-08-12
影响因子：
3.1
作者：
Bhaskaran, M;Chen, HF;Liu, L
通讯作者：
Liu, L