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Zinc stable isotope analysis reveals Zn dyshomeostasis in benign tumours, breast cancer, and adjacent histologically normal tissue.
Metallomics ( IF 2.9 ) Pub Date : 2021-05-31 , DOI: 10.1093/mtomcs/mfab027
Kaj V Sullivan 1, 2 , Rebekah E T Moore 2 , Miles S Capper 2 , Kathrin Schilling 3 , Kate Goddard 4 , Charlotte Ion 4 , Daniel Layton-Matthews 1 , Matthew I Leybourne 1, 5 , Barry Coles 2 , Katharina Kreissig 2 , Olga Antsygina 6, 7 , R Charles Coombes 4 , Fiona Larner 8, 9, 10 , Mark Rehkämper 2
Affiliation  

The disruption of Zn homeostasis has been linked with breast cancer development and progression. To enhance our understanding of changes in Zn homeostasis both inside and around the tumour microenvironment, Zn concentrations and isotopic compositions (δ66Zn) were determined in benign (BT) and malignant (MT) tumours, healthy tissue from reduction mammoplasty (HT), and histologically normal tissue adjacent to benign (NAT(BT)) and malignant tumours (NAT(MT)). Mean Zn concentrations in NAT(BT) are 5.5 µg g-1 greater than in NAT(MT) (p = 0.00056) and 5.1 µg g-1 greater than in HT (p = 0.0026). Zinc concentrations in MT are 12.9 µg g-1 greater than in HT (p = 0.00012) and 13.3 µg g-1 greater than in NAT(MT) (p < 0.0001), whereas δ66Zn is 0.17‰ lower in MT than HT (p = 0.017). Benign tumour Zn concentrations are also elevated compared to HT (p = 0.00013), but are not significantly elevated compared to NAT(BT) (p = 0.32). The δ66Zn of BT is 0.15‰ lower than in NAT(BT) (p = 0.045). The similar light δ66Zn of BT and MT compared to HT and NAT may be related to the isotopic compensation of increased metallothionein (64Zn-rich) expression by activated matrix metalloproteinase (66Zn-rich) in MT, and indicates a resultant 66Zn-rich reservoir may exist in patients with breast tumours. Zinc isotopic compositions thus show promise as a potential diagnostic tool for the detection of breast tumours. The revealed differences of Zn accumulation in healthy and tumour-adjacent tissues require additional investigation.

中文翻译:

锌稳定同位素分析揭示了良性肿瘤、乳腺癌和邻近组织学正常组织中的锌动态平衡。

锌稳态的破坏与乳腺癌的发展和进展有关。为了加深我们对肿瘤微环境内部和周围 Zn 稳态变化的理解,在良性 (BT) 和恶性 (MT) 肿瘤、乳房缩小成形术 (HT) 的健康组织和组织学上测定了 Zn 浓度和同位素组成 (δ66Zn)与良性 (NAT(BT)) 和恶性肿瘤 (NAT(MT)) 相邻的正常组织。NAT(BT) 中的平均锌浓度比 NAT(MT) (p = 0.00056) 高 5.5 µg g-1,比​​ HT (p = 0.0026) 高 5.1 µg g-1。MT 中的锌浓度比 HT (p = 0.00012) 高 12.9 µg g-1,比​​ NAT(MT) 高 13.3 µg g-1 (p < 0.0001),而 MT 中的 δ66Zn 比 HT (p = 0.017)。与 HT 相比,良性肿瘤 Zn 浓度也升高(p = 0. 00013),但与 NAT(BT) 相比没有显着升高(p = 0.32)。BT 的 δ66Zn 比 NAT(BT) 低 0.15‰ (p = 0.045)。与 HT 和 NAT 相比,BT 和 MT 的相似光 δ66Zn 可能与 MT 中活化的基质金属蛋白酶(富含 66Zn)表达增加的金属硫蛋白(富含 64Zn)的同位素补偿有关,并表明由此产生的富含 66Zn 的储层可能存在于乳腺肿瘤患者中。因此,锌同位素组合物有望成为检测乳腺肿瘤的潜在诊断工具。健康和邻近肿瘤组织中锌积累的揭示差异需要进一步研究。与 HT 和 NAT 相比,BT 和 MT 的相似光 δ66Zn 可能与 MT 中活化的基质金属蛋白酶(富含 66Zn)表达增加的金属硫蛋白(富含 64Zn)的同位素补偿有关,并表明由此产生的富含 66Zn 的储层可能存在于乳腺肿瘤患者中。因此,锌同位素组合物有望成为检测乳腺肿瘤的潜在诊断工具。健康和邻近肿瘤组织中锌积累的揭示差异需要进一步研究。与 HT 和 NAT 相比,BT 和 MT 的相似光 δ66Zn 可能与 MT 中活化的基质金属蛋白酶(富含 66Zn)表达增加的金属硫蛋白(富含 64Zn)的同位素补偿有关,并表明由此产生的富含 66Zn 的储层可能存在于乳腺肿瘤患者中。因此,锌同位素组合物有望成为检测乳腺肿瘤的潜在诊断工具。健康和邻近肿瘤组织中锌积累的揭示差异需要进一步研究。因此,锌同位素组合物有望成为检测乳腺肿瘤的潜在诊断工具。健康和邻近肿瘤组织中锌积累的揭示差异需要进一步研究。因此,锌同位素组合物有望成为检测乳腺肿瘤的潜在诊断工具。健康和邻近肿瘤组织中锌积累的揭示差异需要进一步研究。
更新日期:2021-05-10
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