Extracellular vesicle proteomes of two transmissible cancers of Tasmanian devils reveal tenascin-C as a serum-based differential diagnostic biomarker

Cathelicidin-3 Associated With Serum Extracellular Vesicles Enables Early Diagnosis of a Transmissible Cancer

“…In contrast with the likely host origin of CATH3, we found that profilin-1 (PFN1), the overt DFTD biomarker found in this study, was highly expressed in EVs derived from DFTD cells in vitro ( 32 ). As DFTD cells have a Schwann cell origin ( 17 ), the upregulation of the actin-binding protein PFN1 is not surprising as it is required for Schwann cell development and migration ( 44 ).…”

“…As CATH3 was not identified in EVs derived from cultured DFTD tumor cells ( 32 ), we propose that this early DFTD biomarker is likely associated with host cell derived EVs rather than those of tumor origin. EV protein cargo found in plasma/serum of cancer patients reflects the systemic effects of cancer, displaying markers not only associated with the primary tumor, but also the tumor microenvironment, distant organs, and the immune system ( 6 ).…”

“…To evaluate whether the upregulated proteins present in serum of advanced DFTD-infected devils relative to healthy controls were potentially released by DFTD cells, we used a proteomic database of EVs derived from cultured DFTD cells ( 32 ). We found that of the 96 upregulated EV associated proteins derived from serum of DFTD infected devils relative to healthy controls, 19 of them overlapped with the proteins of EVs derived from DFTD cells that were upregulated relative to EVs derived from healthy fibroblasts ( Figure S2 ).…”

“…This is consistent with previous reports that found a strong correlation of general EV markers with advanced cancer stages, indicating their potential prognostic value ( 8 , 51 ). The three proteins myosin heavy chain 10 (MYH10), transforming growth factor beta induced (TGFBI), and connective growth factor (CTGF) with the strongest correlations with tumor volume are not generic EV markers and were not found in EVs derived from DFTD cells in vitro ( 32 ). However, these proteins have all been documented to be associated with aggressiveness of tumor progression.…”

“…To identify possible signals from DFTD tumors, an EV proteome database derived from cultured DFTD cells was used to identify proteins in serum EVs that may originate from DFTD cells ( 32 ). Proteins upregulated in DFTD EVs relative to healthy fibroblast EVs and in EVs derived from serum samples of DFTD-infected devils relative to healthy controls obtained in the discovery cohort were compared.…”