Most human cancers display a dysregulated expression of one or more receptor tyrosine kinases (RTKs). There is strong evidence in the association between altering the RTK’s functions and the rate of cancer progression which has led to novel therapeutic strategies in the treatment of cancer. Although the entire oncogenic process is not completely understood, it has been proved that in pancreatic cancer, a unique RTK known as the Discoidin Domain Receptors (DDRs) specifically binds to and is activated by collagen which in turn plays a role in cancer progression and metastasis by regulating the interactions between the cancer cells and their surrounding environment. DDRs seem to play a key role in the contribution of tumor growth and metastasis in pancreatic cancer by sensing the collagen. Hence, disrupting the DDR-collagen interaction may impact the ability of PC cells to survive. This project investigates the use of advanced technology to measure the interactions within the environment and behavior of DDR on live PC cells. These measurements will be done using a novel nano-mechanical method. An atomic force microscopy (AFM) will be used to investigate protein-protein interactions, in our case, to selectively measure individual surface receptors on live cells interactions to the collagen at a single-molecule level. This will then be translated to binding kinetics of the ligands to receptors as well as capture the DDR density across cells. Matrices with varying mechanical properties will be created using hyaluronic acid and collagen to mimic PC environment and to explore the relationship between stiffness and presence/lack of collagen and expression of DDR on the PC cells. In addition, the morphology and proliferation of both cell lines will be documented on matrices of various stiffnesses with collagen and fibronectin coating. Immunostaining and western blotting will be performed to investigate the presence/absence and quantify the expression of DDR in both cell lines. The mechanics of the hyaluronic acid gel matrixes and pancreatic cancer cell lines were collected. DDR-collagen interactions were isolated, and the association/dissociation rates were quantified. The total DDR protein expression was performed using Western Blot and AFM analysis. The complete results will be presented.

Development of new pancreatic cancer fingerprinting tools

Macromolecular Chemistry: The Second Century

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ACS Spring 2020 National Meeting & Expo

The official archive and repository for all ACS Meetings & Expositions abstracts and select posters or presentations.