title: Role of pancreatic cancer-derived exosomes in salivary biomarker development.
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.
authors.affiliation: From the Dental Research Institute, UCLA School of Dentistry, Los Angeles, California 90095.
authors.forename: Chang
authors.initials: C
authors.lastname: Lau
authors.forename: Yong
authors.initials: Y
authors.lastname: Kim
authors.forename: David
authors.initials: D
authors.lastname: Chia
authors.forename: Nadine
authors.initials: N
authors.lastname: Spielmann
authors.forename: Guido
authors.initials: G
authors.lastname: Eibl
authors.forename: David
authors.initials: D
authors.lastname: Elashoff
authors.forename: Fang
authors.initials: F
authors.lastname: Wei
authors.forename: Yi-Ling
authors.initials: YL
authors.lastname: Lin
authors.forename: Aune
authors.initials: A
authors.lastname: Moro
authors.forename: Tristan
authors.initials: T
authors.lastname: Grogan
authors.forename: Samantha
authors.initials: S
authors.lastname: Chiang
authors.forename: Eric
authors.initials: E
authors.lastname: Feinstein
authors.forename: Christopher
authors.initials: C
authors.lastname: Schafer
authors.forename: James
authors.initials: J
authors.lastname: Farrell
authors.forename: David T W
authors.initials: DT
authors.lastname: Wong
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism*; D045744:Cell Line, Tumor; D004950:Esterases / Q000378:metabolism; D055354:Exosomes / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D046529:Microscopy, Electron, Transmission; D009368:Neoplasm Transplantation; D020411:Oligonucleotide Array Sequence Analysis; D010179:Pancreas / Q000378:metabolism; D010190:Pancreatic Neoplasms / Q000378:metabolism*; D012463:Saliva / Q000378:metabolism*; D059467:Transcriptome
chemical_list: D014408:Biomarkers, Tumor; D004950:Esterases; D000109:Acetylcholine
keywords: Biomarkers; Cancer; Exosomes; Pancreas; Saliva; mRNA