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Specific N-Linked Glycosylation Patterns in Areas of Necrosis in Tumor Tissues
International Journal of Mass Spectrometry ( IF 1.6 ) Pub Date : 2019-03-01 , DOI: 10.1016/j.ijms.2018.01.002
Danielle A Scott 1, 2, 3 , Kim Norris-Caneda 1, 2, 3 , Laura Spruill 1, 2, 3 , Evelyn Bruner 1, 2, 3 , Yuko Kono 1, 2, 3 , Peggi M Angel 1, 2, 3 , Anand S Mehta 1, 2, 3 , Richard R Drake 1, 2, 3
Affiliation  

Tissue necrosis is a form of cell death common in advanced and aggressive solid tumors, and is associated with areas of intratumoral chronic ischemia. The histopathology of necrotic regions appear as a scaffold of cellular membrane remnants, reflective of the hypoxia and cell degradation events associated with this cellular death pathway. Changes in the glycosylation of cell surface proteins is another common feature of cancer progression. Using a recently developed mass spectrometry imaging approach to evaluate N-linked glycan distributions in human formalin-fixed clinical cancer tissues, differences in the glycan structures of regions of tumor, stroma and necrosis were evaluated. While the structural glycan classes detected in the tumor and stromal regions are typically classified as high mannose or branched glycans, the glycans found in necrotic regions displayed limited branching, contained sialic acid modifications and lack fucose modifications. While this phenomenon was initially classified in breast cancer tissues, it has been also seen in cervical, thyroid and liver cancer samples. These changes in glycosylation within the necrotic regions could provide further mechanistic insight to necrotic changes in cancer tissue and provide new research directions for identifying prognostic markers of necrosis.

中文翻译:

肿瘤组织坏死区域中特定的 N 联糖基化模式

组织坏死是晚期和侵袭性实体瘤中常见的一种细胞死亡形式,与肿瘤内慢性缺血区域有关。坏死区域的组织病理学表现为细胞膜残余物的支架,反映了与这种细胞死亡途径相关的缺氧和细胞降解事件。细胞表面蛋白糖基化的变化是癌症进展的另一个常见特征。使用最近开发的质谱成像方法来评估人福尔马林固定的临床癌症组织中的 N-连接聚糖分布,评估了肿瘤、基质和坏死区域的聚糖结构的差异。虽然在肿瘤和基质区域检测到的结构聚糖类别通常被归类为高甘露糖或支链聚糖,在坏死区域发现的聚糖显示出有限的分支,包含唾液酸修饰并且缺乏岩藻糖修饰。虽然这种现象最初被归类在乳腺癌组织中,但它也出现在宫颈癌、甲状腺癌和肝癌样本中。坏死区域内糖基化的这些变化可以提供对癌组织坏死变化的进一步机制洞察,并为鉴定坏死的预后标志物提供新的研究方向。
更新日期:2019-03-01
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