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

Abstract

AbstractPancreatic 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 ECM on PDAC cell lines by culturing the cells on surfaces coated with different ECM proteins. Our data showed that the primary tumor-derived cell lines have different morphology that depends on the ECM proteins on which they are cultured, while metastatic lesion-derived PDAC lines’ morphology does not change with respect to the different ECM proteins. Similarly, ECM proteins also modulate the proliferation rate and the gemcitabine sensitivity of the primary tumor PDAC cell lines, but not for the metastatic PDAC lines. Lastly, transcriptomics analysis of the primary tumor PDAC cells cultured on different ECM proteins 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.