Differential roles of extracellular matrix proteins on primary and metastatic pancreatic cancer cells

Pancreatic cancer adenocarcinoma (PDAC) has been reported to be the third highest cause of cancer-related deaths in the United States. PDAC is known for its high proportion of stroma which accounts for 90% of the tumor mass. The stroma is made up of extracellular matrix (ECM) and non-malignant cells such as inflammatory cells, cancer-associated fibroblasts (CAF), and lymphatic and blood vessels. Here, we decoupled the roles of the extracellular matrix on PDAC cell lines by investigating the effects of different ECM proteins on the cell lines. Our data showed that primary lines have different morphology that depends on the ECM proteins on which they are cultured, while metastatic PDAC lines’ morphology does not change with respect to different ECM proteins. Next, we examined how these ECM proteins affect the cell response to the gemcitabine’s cytotoxicity. Lastly, transcriptomics analysis of the cells cultured on different ECM reveals the regulation of various pathways, such as cell cycle, cell adhesion molecules, and focal adhesion, including the regulation of several integrin genes that are essential for ECM recognition.