Cancer patients diagnosed with pancreatic adenocarcinoma have low 5-year survival rates in the United States. One of the reasons for this is the excessive accumulation of extracellular matrix (ECM) proteins in the tumor tissues. It is expected that lowering the ECM in the tumors makes it more accessible to chemotherapeutic interventions and improves the patient's survival rate. Thus, testing whether lowering the expression of an ECM receptor, integrin β1, reduces the ECM in pancreatic cancer cell lines is the objective of this study. Integrin β1 protein inhibition was done using shRNA plasmids in pancreatic cancer cell line PANC-1. Clones with lower integrin β1 proteins were developed using puromycin selection and characterized by qRT-PCR and western blotting. A Matrigel assay was run to determine differences in tumor growth in the 3D microenvironment. The function of the cells was determined with cell spreading and adhesion assays showed significant decrease in the PANC-1 integrin β1 shRNA clones compared to control shRNA-treated cells. Our studies found that decreasing the expression of integrin β1 reduced protein levels of integrin α5, vitronectin, and fibronectin in the PANC-1 cells. These results suggest the importance of integrin β1 in cancer cell adhesion, spreading, desmoplasia, and tumor cell growth. This program is supported by an Institutional Development Award (IDeA) from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM103442.
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Fernholz et al. (2024) studied this question.
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