Abstract A065: Upregulated expression of bulky glycoproteins modulates integrin-based adhesions in pancreatic cancer cells

Abstract With a 5-year survival rate of about 10%, pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer-related deaths in the United States. Compared to other carcinomas, PDAC is highly desmoplastic, which leads to aberrant integrin adhesion complexes (IACs) and altered integrin-based signaling, contributing to PDAC’s aggressive nature. Therefore, we seek to characterize IACs throughout PDAC’s malignancy progression, focusing on how the glycocalyx composition and the intratumoral environment impact IAC structure. To investigate this, we enzymatically degraded several aberrantly expressed glycocalyx components in PDAC: mucins, sialic acids, hyaluronic acid, and N-glycans. Then we used confocal microscopy to visualize differences in IAC structure across various representative pancreatic cancer cell lines. We observed cell line-dependent alterations in IAC distribution, size, and length. Our results suggest that IAC distribution and size change as PDAC progresses and encounters different physiological cues, thus possibly impacting integrin-based signaling. Following glycocalyx-targeting treatments, cleaving mucins appears to significantly decrease individual IAC size and total IAC area. Cleaving hyaluronic acid, sialic acids, and N-glycans did not significantly affect individual IAC size or total IAC area. This indicates that a more complex glycocalyx-IAC regulatory axis exists, rather than solely a kinetic trap imposed by the glycocalyx’s thickness and density. Future studies will proceed in two main directions. First, we will investigate how PDAC stages and glycocalyx treatments affect cellular mechanics such as cell traction forces and cell-ECM (extracellular matrix) adhesion strength. Second, we will elucidate the role of intratumoral mechanics and ECM on controlling IACs throughout PDAC malignancy progression. Citation Format: Elijah Marquez, Andrew Massey, Alexander Cartagena-Rivera. Upregulated expression of bulky glycoproteins modulates integrin-based adhesions in pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research—Emerging Science Driving Transformative Solutions; Boston, MA; 2025 Sep 28-Oct 1; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2025;85(18_Suppl_3):Abstract nr A065.