Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development
Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development
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DOI：
10.1074/jbc.m113.452458
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发表时间：
2013-09-13
影响因子：
4.8
通讯作者：
Wong, David T. W.
中科院分区：
文献类型：
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作者：
Lau, Chang;Kim, Yong;Wong, David T. W.
最近的研究表明，在胰腺癌、乳腺癌、肺癌和卵巢癌等系统性疾病的发展过程中，可以很容易地检测到歧视性唾液生物标志物。然而，唾液生物标记物用于检测系统性疾病的有效性已被削弱，这是因为缺乏生物学和机制上的理由来解释为什么口腔远端疾病会导致唾液中歧视性生物标记物的发展。在这里，我们检验了胰腺肿瘤来源的外切体机械地参与胰腺癌-歧视性唾液转录生物标记物的发展的假设。我们首先建立了胰腺癌小鼠模型，通过将小鼠胰腺癌细胞系Panc02移植到同基因宿主C57BL/6的胰腺中来产生歧视性唾液生物标记物。然后通过设计抑制外切体生物发生的Panc02细胞系，植入C56BL/6小鼠体内，并检查歧视性唾液生物标记物是否被消融或破坏，来检验胰腺癌来源的外切体在鉴别唾液生物标记物形成中的作用。抑制外切体的生物发生会导致歧视性唾液生物标记物发育的消融。这项研究支持，肿瘤来源的外切体在唾液和远端系统疾病中提供了一种识别生物标记物的机制。
Recent studies have demonstrated that discriminatory salivary biomarkers can be readily detected upon the development of systemic diseases such as pancreatic cancer, breast cancer, lung cancer, and ovarian cancer. However, the utility of salivary biomarkers for the detection of systemic diseases has been undermined due to the absence of the biological and mechanistic rationale as to why distal diseases from the oral cavity would lead to the development of discriminatory biomarkers in saliva. Here, we examine the hypothesis that pancreatic tumor-derived exosomes are mechanistically involved in the development of pancreatic cancer-discriminatory salivary transcriptomic biomarkers. We first developed a pancreatic cancer mouse model that yielded discriminatory salivary biomarkers by implanting the mouse pancreatic cancer cell line Panc02 into the pancreas of the syngeneic host C57BL/6. The role of pancreatic cancer-derived exosomes in the development of discriminatory salivary biomarkers was then tested by engineering a Panc02 cell line that is suppressed for exosome biogenesis, implanting into the C56BL/6 mouse, and examining whether the discriminatory salivary biomarker profile was ablated or disrupted. Suppression of exosome biogenesis results in the ablation of discriminatory salivary biomarker development. This study supports that tumor-derived exosomes provide a mechanism in the development of discriminatory biomarkers in saliva and distal systemic diseases.