Abstract
Abstract Pancreatic Ductal Adenocarcinoma (PDAC) is a highly lethal malignancy with a 5-year survival rate around 10% due to late detection and therapeutic resistance. Thus, new methods to detect PDAC earlier in high-risk and general populations are greatly needed. Early detection tests have historically relied on circulating nucleic acids or proteins that have been identified as enriched in patients with PDAC by large-scale studies, but they often lack a firm basic biological context that would bolster the sensitivity and specificity of these tests. To this end, we have introduced a construct into PDAC organoid and 2D lines that enables the labeling of PDAC-secreted proteins with biotin (Sec61-BioID) in vitro and in vivo. With this system, we can specifically isolate the PDAC secretome and identify the proteins via mass spectrometry. From this approach, we have identified Gelsolin (GSN), an enzyme that regulates actin dynamics, as a highly secreted protein by a panel of PDAC cell lines in vitro and in vivo. We have explored the biological role of secreted GSN in PDAC tumorigenesis via CRISPR knockout. GSN knockout abrogated the growth of PDAC tumors in NSG mice, and we are delineating the potential mechanisms that explain this defect via histological analysis and in vitro cell proliferation and invasion assays. Additionally, we have analyzed purified secreted GSN from PDAC lines by mass spectrometry to identify potential post-translational modifications that may differentiate PDAC-derived GSN from other GSN molecules, secreted by healthy tissue, in circulation. We are currently utilizing biochemical approaches to validate these putative modifications and define their specificity in PDAC patient blood as compared to healthy age-matched controls. Citation Format: Jonathan P. Kastan, Oliver Standring, Paolo Cifani, Victoria Gaeth, Amanda Jensen, Youngkyu Park, David Tuveson. Secretome labeling identifies gelsolin as a potential pro-tumorigenic PDAC biomarker [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Pancreatic Cancer; 2023 Sep 27-30; Boston, Massachusetts. Philadelphia (PA): AACR; Cancer Res 2024;84(2 Suppl):Abstract nr B008.
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
