Role of Pancreatic Cancer-derived Exosomes in Salivary Biomarker Development

Chang S. Lau(University of California, Los Angeles), Yong Kim(University of California, Los Angeles), David Chia, Nadine Spielmann(University of California, Los Angeles), Guido Eibl(Center for Excellence in Education), David Elashoff, Fang Wei(University of California, Los Angeles), Yi‐Ling Lin(University of California, Los Angeles), Aune Moro(Center for Excellence in Education), Tristan Grogan, Samantha Chiang(University of California, Los Angeles), Eric Feinstein(University of California, Los Angeles), Christopher A. Schafer(University of California, Los Angeles), James J. Farrell(University of California, Los Angeles), David T. Wong(University of California, Los Angeles)
Journal of Biological Chemistry
July 24, 2013
10.1074/jbc.m113.452458
Cited by 253Open Access
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Abstract

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.

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