A Structural Analysis of Glycosaminoglycans from Lethal and Nonlethal Breast Cancer Tissues: Toward a Novel Class of Theragnostics for Personalized Medicine in Oncology?
A Structural Analysis of Glycosaminoglycans from Lethal and Nonlethal Breast Cancer Tissues: Toward a Novel Class of Theragnostics for Personalized Medicine in Oncology?
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DOI：
10.1089/omi.2011.0102
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发表时间：
2012-03-01
影响因子：
3.3
通讯作者：
Linhardt, Robert J.
中科院分区：
文献类型：
--
作者：
Weyers, Amanda;Yang, Bo;Linhardt, Robert J.
癌症是对发达国家和发展中国家都有巨大影响的主要非传染性疾病之一。全球公共卫生和癌症患者的个性化医疗迫切需要真正创新的诊断方法，以告知疾病易感性、预后和/或对治疗的反应（治疗不确定性）。本研究检测了6例患者的致死性和非致死性乳腺癌组织中糖胺聚糖（GAG）的结构和含量。从含有致死性癌症肿瘤的组织中分离的糖胺聚糖含量约为其他组织的两倍。分子量分析表明，来自癌组织的糖胺聚糖的重均链长平均增加了5个二糖单位，增加了约15%。Dissacharide分析发现癌组织和正常组织之间的硫酸化模式存在差异，以及从致死性和非致死性癌症患者中分离的GAG链的硫酸化差异。具体地，癌组织显示CS链的“6S”位置处的硫酸化增加和HS二糖NSCS水平的增加。患有致命癌症的患者显示HS硫酸化减少，具有较低水平的“6S”和较高水平的未硫酸化的“0 S”二糖。虽然这些发现来自有限的样本量，但它们表明GAG的结构变化存在于癌组织和非癌组织之间，以及高度转移性癌症患者的组织和通过化疗成功治疗的癌症之间。基于这些发现，我们假设：（1）随着组织癌变，身体的GAG结构发生了推定的变化;（2）GAG组成中可能存在先天的结构性个体差异，这些差异有助于某些患者发生癌症时的肿瘤转移。
Cancer is one of the leading noncommunicable diseases that vastly impacts both developed and developing countries. Truly innovative diagnostics that inform disease susceptibility, prognosis, and/or response to treatment (theragnostics) are seriously needed for global public health and personalized medicine for patients with cancer. This study examined the structure and content of glycosaminoglycans (GAGs) in lethal and nonlethal breast cancer tissues from six patients. The glycosaminoglycan content isolated from tissue containing lethal cancer tumors was approximately twice that of other tissues. Molecular weight analysis showed that glycosaminoglycans from cancerous tissue had a longer weight average chain length by an average of five disaccharide units, an increase of approximately 15%. Dissacharide analysis found differences in sulfation patterns between cancerous and normal tissues, as well as sulfation differences in GAG chains isolated from patients with lethal and nonlethal cancer. Specifically, cancerous tissue showed an increase in sulfation at the "6S" position of CS chains and an increase in the levels of the HS disaccharide NSCS. Patients with lethal cancer showed a decrease in HS sulfation, with lower levels of "6S" and higher levels of the unsulfated "0S" disaccharide. Although these findings come from a limited sample size, they indicate that structural changes in GAGs exist between cancerous and noncancerous tissues and between tissues from patients with highly metastatic cancer and cancer that was successfully treated by chemotherapy. Based on these findings, we hypothesize that (1) there are putative changes in the body's construction of GAGs as tissue becomes cancerous; (2) there may be innate structural person-to-person variations in GAG composition that facilitate the metastasis of tumors in some patients when they develop cancer.