GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors.
GLUT3/SLC2A3 Is an Endogenous Marker of Hypoxia in Prostate Cancer Cell Lines and Patient-Derived Xenograft Tumors.
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DOI：
10.3390/diagnostics12030676
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发表时间：
2022-03-10
期刊：
影响因子：
--
通讯作者：
Rogers GC
中科院分区：
文献类型：
--
作者：
Ryniawec JM;Coope MR;Loertscher E;Bageerathan V;de Oliveira Pessoa D;Warfel NA;Cress AE;Padi M;Rogers GC
实体肿瘤的微环境是动态的，通常包含低氧水平(低氧)的小袋，周围是含氧组织。事实上，受损的血管系统是肿瘤微环境的一个标志，造成氧气供应的空间梯度和时间变异性。值得注意的是，低氧与患者转移增加和生存不良有关。因此，为了帮助治疗决策和更好地了解缺氧在癌症进展中的作用，识别缺氧的内源性生物标志物对于人类组织中的空间表型致癌病变至关重要，无论是癌前病变、良性病变还是恶性病变。在这里，我们将葡萄糖转运蛋白GLUT3/SLC2A3描述为缺氧性前列腺上皮细胞和前列腺癌的生物标志物。对非致癌、永生化的前列腺上皮细胞的转录分析显示，在低氧条件下，GLUT3的表达显著增加。此外，GLUT3蛋白在培养的低氧前列腺细胞系中增加2.4倍，并在异种移植瘤的缺氧区上调，包括两个患者来源的异种移植物(PDX)。最后，GLUT3优于其他已建立的缺氧标志物；与GLUT1和CA9抗体的混合物相比，PDX标本中的GLUT3染色检测到的肿瘤面积是GLUT1和CA9混合抗体的2.6-8.3倍。因此，鉴于肿瘤的异质性，我们建议在检测前列腺样本中的缺氧区时，将GLUT3添加到免疫染色面板中。
The microenvironment of solid tumors is dynamic and frequently contains pockets of low oxygen levels (hypoxia) surrounded by oxygenated tissue. Indeed, a compromised vasculature is a hallmark of the tumor microenvironment, creating both spatial gradients and temporal variability in oxygen availability. Notably, hypoxia associates with increased metastasis and poor survival in patients. Therefore, to aid therapeutic decisions and better understand hypoxia’s role in cancer progression, it is critical to identify endogenous biomarkers of hypoxia to spatially phenotype oncogenic lesions in human tissue, whether precancerous, benign, or malignant. Here, we characterize the glucose transporter GLUT3/SLC2A3 as a biomarker of hypoxic prostate epithelial cells and prostate tumors. Transcriptomic analyses of non-tumorigenic, immortalized prostate epithelial cells revealed a highly significant increase in GLUT3 expression under hypoxia. Additionally, GLUT3 protein increased 2.4-fold in cultured hypoxic prostate cell lines and was upregulated within hypoxic regions of xenograft tumors, including two patient-derived xenografts (PDX). Finally, GLUT3 out-performs other established hypoxia markers; GLUT3 staining in PDX specimens detects 2.6–8.3 times more tumor area compared to a mixture of GLUT1 and CA9 antibodies. Therefore, given the heterogeneous nature of tumors, we propose adding GLUT3 to immunostaining panels when trying to detect hypoxic regions in prostate samples.
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影响因子：
5.5
作者：
Baumann, Marc U.;Zamudio, Stacy;Illsley, Nicholas P.
通讯作者：
Illsley, Nicholas P.
影响因子：
4.4
作者：
Custódio TF;Paulsen PA;Frain KM;Pedersen BP
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Pedersen BP
影响因子：
3.6
作者：
Corn, PG;Ricci, MS;El-Deiry, WS
通讯作者：
El-Deiry, WS
影响因子：
5.2
作者：
Bader SB;Dewhirst MW;Hammond EM
通讯作者：
Hammond EM
DOI：
10.1073/pnas.95.20.11715
发表时间：
1998-09-29
影响因子：
11.1
作者：
Chandel, NS;Maltepe, E;Schumacker, PT
通讯作者：
Schumacker, PT