Abstract A001: Improved Modeling of Pancreatic Ductal Adenocarcinoma (PDAC) Using High-Density Collagen Matrix
Marc Abou Assali, Kim Nguyen-Ta, Sural Ranamukhaarachchi, Himangshu Sonowal, Utsav Joshi, Jorge De La Torre Medina, Brian Ton, Badri Narayanan Narasimhan, Jeffrey Turner, Adam Klie, Maleeha Madinawala, Hannah Carter, Stephanie Fraley, Rebekah WhiteAbstract
Background:
Pancreatic Ductal Adenocarcinoma (PDAC) has a tumor microenvironment (TME) that is rich in organized strands of type I collagen. The most commonly used PDAC models utilize basement membrane extract (BME, e.g. Matrigel), which instead contains the more pliable type IV collagen. We hypothesize that utilizing a high-density collagen (HDC) matrix, made up of type I collagen, will improve the modeling of PDAC for translational work.
Methods:
Murine (KPC1199 and KPC4580) and human (KP4 and DANG) PDAC cell lines were cultured in vitro in either a BME or HDC matrix for seven days. Western blot analyses of mesenchymal markers (e.g. vimentin), as well as analyses of circularity were subsequently performed. In addition, KPC1199 and KPC4580 cells were implanted orthopically into the pancreatic tails of syngeneic C57BL/6J mice in either BME or HDC, with tumors analyzed after five weeks for metastasis and collagen content.
Results:
Western blot analysis suggests increased vimentin expression along with isoform heterogeneity in the HDC cells. In addition, the HDC-grown cells demonstrated a more invasive phenotype with decreased circularity, more collagen content in the in vivo TME, and increased liver metastases with orthotopic implantation than BME-grown cells.
Conclusions:
Our study suggests that tumors established using HDC-based gel matrices demonstrate PDAC characteristics more analogous to the human PDAC TME and metastatic behavior that is expected of this challenging disease.
Citation Format:
Marc Abou Assali, Kim Nguyen-Ta, Sural Ranamukhaarachchi, Himangshu Sonowal, Utsav Joshi, Jorge De La Torre Medina, Brian Ton, Badri Narayanan Narasimhan, Jeffrey Turner, Adam Klie, Maleeha Madinawala, Hannah Carter, Stephanie Fraley, Rebekah White. Improved Modeling of Pancreatic Ductal Adenocarcinoma (PDAC) Using High-Density Collagen Matrix [abstract]. In: Proceedings of the AACR Conference on Pancreatic Cancer: New Frontiers in Biology and Therapeutic Development; 2026 Sep 25-28; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(18_Suppl_2):Abstract nr A001.