Abstract
Abstract Pancreatic cancer is one of the most lethal malignancies with a 5-year survival rate currently below 10%. Unfortunately, current diagnostic methods are unable to readily recognize early disease progression, and symptoms are commonly misdiagnosed. Therefore, determining novel biomarkers related to disease progression remains an important area of research. Transmembrane mucins, a major component of the cellular glycocalyx, normally play a protective role in epithelial tissues; they are also known to be overexpressed in various cancers, including pancreatic. In addition, mucins are known to increase aggressiveness, enhance drug resistance, and reduce survivability in cancers where they are upregulated. Although the biochemical effects of mucins are well understood, there is minimal research into how they affect cancer cells at a biophysical level. Recently, there has been great interest in examining the biophysical properties of cancer cells. The current consensus is that cancerous cells are softer than their normal counterparts, and that more metastatic cells become softer compared to more benign tumor cells. Measuring these physical properties could potentially give clinicians a more rapid way to diagnose tumors, determine the course of disease progression, physically determine the effect of a biomolecule when its expression is altered, or determine the efficacy of various chemotherapeutics. In this study, we will first use atomic force microscopy-based nanomechanical mapping to measure the biophysical differences between normal cells, cancerous cells, and the extracellular matrix extracted from human patient tumor tissues and track the measured changes, both before and after chemo treatments. Our preliminary in vitro results suggest that 2D-adherent human cancerous pancreatic cells are indeed softer than their normal counterparts, in agreement with the literature. In addition, modulation of the glycocalyx architecture via hyaluronidase treatment leads to considerable changes in cellular stiffness in both normal and cancerous cells, implying a link between the glycocalyx and the underlying actomyosin skeleton. Future studies will examine the in vitro effects of specific transmembrane mucins. Using overexpression and knockdown transfection models, the impact on cellular mechanics, as well as structural changes in the glycocalyx and actomyosin cortex, will be analyzed in pancreatic cancer cells to determine how these mucins effect cellular mechanics and by extension regulate tumorigenesis and metastasis. Citation Format: Andrew Massey. Mechanobiological analysis of human patient pancreatic cancer tissues and the effect of cellular transmembrane mucins on glycocalyx-actomyosin mechanics [abstract]. In: Proceedings of the AACR Virtual Special Conference on Pancreatic Cancer; 2021 Sep 29-30. Philadelphia (PA): AACR; Cancer Res 2021;81(22 Suppl):Abstract nr PO-044.
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