FAP-overexpressing fibroblasts enhance pancreatic cancer cell invasion
Author Information
Author(s): Lee Hyung-Ok, Mullins Stefanie R, Franco-Barraza Janusz, Valianou Matthildi, Cukierman Edna, Cheng Jonathan D
Primary Institution: Fox Chase Cancer Center
Hypothesis
FAP enzymatic activity locally modifies stromal ECM components thus facilitating the formation of a permissive microenvironment promoting tumor invasion in human pancreatic cancer.
Conclusion
Disruption of FAP activity and β1-integrins may abrogate the invasive capabilities of pancreatic and other tumors by disrupting the FAP-directed organization of stromal ECM.
Supporting Evidence
- FAP remodels the ECM through modulating protein levels and increasing fibronectin and collagen fiber organization.
- FAP-dependent alterations of the ECM promote tumor invasion along characteristic parallel fiber orientations.
- Inhibition of FAP enzymatic activity during matrix production results in disorganization of the ECM and impeded tumor invasion.
- The FAP+ matrix-induced tumor invasion phenotype is β1-integrin/FAK mediated.
Takeaway
Fibroblasts that produce a protein called FAP help cancer cells move and invade better. If we can stop FAP, we might stop the cancer from spreading.
Methodology
A tetracycline-inducible FAP overexpressing fibroblastic cell line was generated to study matrix-induced cancer cell behaviors in a 3D matrix system.
Statistical Information
P-Value
p = 0.009, p = 0.002, p = 0.001
Statistical Significance
p<0.001
Digital Object Identifier (DOI)
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